120 results on '"Alison G. Freifeld"'
Search Results
2. Bloodstream Infections in Hematologic Malignancy Patients With Fever and Neutropenia: Are Empirical Antibiotic Therapies in the United States Still Effective?
- Author
-
Andrea J Zimmer, Erica Stohs, Jane Meza, Christopher Arnold, John W Baddley, Pranatharthi Chandrasekar, Zeinab El Boghdadly, Carlos A Gomez, Eileen K Maziarz, Jose G Montoya, Steven Pergam, Kenneth V Rolston, Michael J Satlin, Gowri Satyanarayana, Shmuel Shoham, Lynne Strasfeld, Randy Taplitz, Thomas J Walsh, Jo-Anne H Young, Yuning Zhang, and Alison G Freifeld
- Subjects
Infectious Diseases ,Oncology - Abstract
Background Rising antimicrobial resistance rates may impact the efficacy of empirical antibiotic treatment for febrile neutropenia in high-risk cancer patients. Lacking contemporary data about the epidemiology, antibiotic resistance patterns, and clinical outcomes from bloodstream infections (BSIs) in US cancer patients, it is unclear if current guidelines remain relevant. Methods In a cross-sectional study, 14 US cancer centers prospectively identified BSIs in high-risk febrile neutropenic (FN) patients, including those receiving chemotherapy for hematologic malignancies or hematopoietic stem cell transplantation. Results Among 389 organisms causing BSI in 343 patients, there was an equal distribution of gram-negative (GN) and gram-positive (GP) bacteria, with variability across centers. Cefepime and piperacillin-tazobactam were the most commonly prescribed empirical antibiotics for FN, at 62% and 23%, respectively; a GP-directed agent was empirically included in nearly half of all FN episodes within the first 24 hours. Susceptibility to fluoroquinolones, cefepime, piperacillin-tazobactam, and carbapenems was 49%, 84%, 88%, and 96%, respectively, among GN isolates. Critical illness (CrI), defined as a new requirement for mechanical ventilation, vasopressor, or death within 30 days, occurred in 15% and did not correlate with fluoroquinolone prophylaxis, organism type, initial antibiotics, or adequacy of coverage. Only severity of illness at presentation, signified by a Pitt bacteremia score ≥2, predicted for critical illness within 30 days. Mortality was 4% by day 7 and 10% overall. Conclusions In accordance with US guidelines, cefepime or piperacillin-tazobactam remain effective agents or empirical treatment for high-risk cancer patients with FN who are stable at presentation, maintaining high GN pathogen susceptibility and yielding excellent outcomes.
- Published
- 2022
3. De-escalation of empiric broad spectrum antibiotics in hematopoietic stem cell transplant recipients with febrile neutropenia
- Author
-
Lindsey Rearigh, Andrea Zimmer, Alison G. Freifeld, and Erica J Stohs
- Subjects
Male ,medicine.medical_specialty ,medicine.drug_class ,medicine.medical_treatment ,Febrile neutropenia ,Antibiotics ,Hematopoietic stem cell transplantation ,Infections ,Disease-Free Survival ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,law ,Internal medicine ,medicine ,Humans ,Decompensation ,Autografts ,Retrospective Studies ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,General Medicine ,Middle Aged ,Allografts ,medicine.disease ,Intensive care unit ,De-escalation ,Anti-Bacterial Agents ,Survival Rate ,030220 oncology & carcinogenesis ,Absolute neutrophil count ,Female ,Original Article ,Complication ,business ,Broad spectrum antibiotic ,030215 immunology - Abstract
Febrile neutropenia (FN) is a common serious complication in patients undergoing hematopoietic stem cell transplantation (HSCT) requiring urgent evaluation and initiation of empiric broad spectrum antibiotics (BSA). The appropriate duration of BSA for FN in patients with negative cultures and no identifiable infection remains undefined. We retrospectively analyzed allogenic and autologous HSCT patients with FN and negative infectious work-up at our facility from 2012 to 2018. The early de-escalation group (EDG) included those who had BSA de-escalation to fluoroquinolone prophylaxis at least 24 h prior to absolute neutrophil count (ANC) recovery after the patient was fever-free for at least 48 h. Among 297 patients undergoing their first HSCT who experienced FN with negative infectious work-up, 83 patients were de-escalated early with the remaining 214 in the standard of care group (SCG) whose BSA were continued until ANC was > 500. Duration of broad-spectrum antibiotics was shorter in EDG compared to SCG (3.86 days vs. 4.62 days, p = 0.03). Rates of mortality, new infections, and clinical decompensation requiring intensive care unit transfer and/or pressor use within 30 days were all similar between the two groups (0% vs. 0.4% p = 1.00, 0% vs. 1.4% p = 0.56, 13.2% vs. 8.4% p = 0.27). This indicates that it is safe to de-escalate antibiotics prior to ANC recovery, leading to less BSA exposure.
- Published
- 2020
4. Safety at the Time of the COVID-19 Pandemic: How to Keep Our Oncology Patients and Healthcare Workers Safe
- Author
-
Matthew A. Lunning, Rafael Fonseca, Dori Klemanski, Kim Slusser, Hope E. Uronis, James J. Bachman, Lawrence N. Shulman, Asmita Mishra, Catherine Liu, Pelin Cinar, Alison G. Freifeld, and Timothy Kubal
- Subjects
Coronavirus disease 2019 (COVID-19) ,business.industry ,Transmission (medicine) ,Social distance ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Disease ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,Pandemic ,Health care ,Medicine ,Oncology patients ,030212 general & internal medicine ,Medical emergency ,business - Abstract
The novel coronavirus, SARS-CoV-2, was first detected as a respiratory illness in December 2019 in Wuhan City, China. Since then, coronavirus disease 2019 (COVID-19) has impacted every aspect of our lives worldwide. In a time when terms such as social distancing and flattening the curve have become a part of our vernacular, it is essential that we understand what measures can be implemented to protect our patients and healthcare workers. Undoubtedly, healthcare providers have had to rapidly alter care delivery models while simultaneously acknowledging the crucial unknowns of how these changes may affect clinical outcomes. This special feature reviews strategies on how to mitigate transmission of COVID-19 in an effort to reduce morbidity and mortality associated with the disease for patients with cancer without infection, for patients with cancer with COVID-19 infection, and for the healthcare workers caring for them, while continuing to provide the best possible cancer care. [Editor’s Note: This article includes the most current information available at time of publication; however, recommendations regarding public safety and practice may change rapidly in this situation. Individuals should get the most up to date information from the CDC website.]
- Published
- 2020
5. Lack of Efficacy of High-Titered Immunoglobulin in Patients with West Nile Virus Central Nervous System Disease
- Author
-
Jared Spotkov, Ilet Dale, Kenneth L. Tyler, John Hart, Yufeng Li, Richard J. Whitley, Martha I. Buitrago, Amy Guillet Agrawal, Jorge Reyno, Alison G. Freifeld, Fred D. Lakeman, John W. Gnann, Diane Hanfelt-Goade, Paul J. Carson, Henry Masur, Inmaculada Aban, Thomas C. Moore, and Penelope Jester
- Subjects
Male ,Epidemiology ,encephalitis ,viruses ,medicine.medical_treatment ,lcsh:Medicine ,Antibodies, Viral ,0302 clinical medicine ,flavivirus ,Omr-IgG-am ,Clinical endpoint ,Medicine ,030212 general & internal medicine ,Saline ,biology ,Lack of Efficacy of High-Titered Immunoglobulin in Patients with West Nile Virus Central Nervous System Disease ,Mortality rate ,Polygam ,Immunoglobulins, Intravenous ,virus diseases ,Middle Aged ,Flavivirus ,Treatment Outcome ,Infectious Diseases ,Population study ,Female ,Antibody ,West Nile virus ,Encephalitis ,Adult ,Microbiology (medical) ,medicine.medical_specialty ,central nervous system disease ,030231 tropical medicine ,neuroinvasive disease ,lcsh:Infectious and parasitic diseases ,Central nervous system disease ,03 medical and health sciences ,WNV ,Internal medicine ,Humans ,lcsh:RC109-216 ,Aged ,business.industry ,Research ,lcsh:R ,medicine.disease ,biology.organism_classification ,Antibodies, Neutralizing ,United States ,Immunoglobulin G ,North America ,Central Nervous System Viral Diseases ,biology.protein ,business ,immunoglobulin ,West Nile Fever - Abstract
Immunoglobulin administered to adults with neuroinvasive disease appeared to be safe but was not demonstrated to improve clinical outcomes., West Nile Virus (WNV) can result in clinically severe neurologic disease. There is no treatment for WNV infection, but administration of anti-WNV polyclonal human antibody has demonstrated efficacy in animal models. We compared Omr-IgG-am, an immunoglobulin product with high titers of anti-WNV antibody, with intravenous immunoglobulin (IVIG) and normal saline to assess safety and efficacy in patients with WNV neuroinvasive disease as part of a phase I/II, randomized, double-blind, multicenter study in North America. During 2003–2006, a total of 62 hospitalized patients were randomized to receive Omr-IgG-am, standard IVIG, or normal saline (3:1:1). The primary endpoint was medication safety. Secondary endpoints were morbidity and mortality, measured using 4 standardized assessments of cognitive and functional status. The death rate in the study population was 12.9%. No significant differences were found between groups receiving Omr-IgG-am compared with IVIG or saline for either the safety or efficacy endpoints.
- Published
- 2019
6. Antimicrobial Stewardship in Cancer Patients: The Time is Now
- Author
-
Samuel L. Aitken, Alison G. Freifeld, Jerod Nagel, Jason N. Barreto, Frank P. Tverdek, Steven A. Pergam, Susan K. Seo, Sanjeet Dadwal, Lilian M. Abbo, William Alegria, and Rupali Jain
- Subjects
medicine.medical_specialty ,business.industry ,MEDLINE ,Cancer ,medicine.disease ,Anti-Bacterial Agents ,Antimicrobial Stewardship ,Oncology ,Neoplasms ,Humans ,Medicine ,Antimicrobial stewardship ,business ,Intensive care medicine - Published
- 2019
7. Optimal Management of Neutropenic Fever in Patients With Cancer
- Author
-
Andrea Zimmer and Alison G. Freifeld
- Subjects
medicine.medical_specialty ,medicine.drug_class ,Antibiotics ,Population ,Drug resistance ,03 medical and health sciences ,0302 clinical medicine ,Antibiotic resistance ,Neoplasms ,medicine ,Humans ,030212 general & internal medicine ,Chemotherapy-Induced Febrile Neutropenia ,Intensive care medicine ,education ,education.field_of_study ,Oncology (nursing) ,business.industry ,Health Policy ,Cancer ,Drug Resistance, Microbial ,medicine.disease ,Optimal management ,Anti-Bacterial Agents ,Oncology ,030220 oncology & carcinogenesis ,business ,Complication ,Febrile neutropenia - Abstract
Febrile neutropenia remains an important complication of treatment with cytotoxic chemotherapy. It is often the first and sometimes the only sign or symptom of infection in this vulnerable patient population. Urgent and appropriate evaluation and treatment are imperative because delay in initiating appropriate antibiotic therapy may be life threatening. Selection of antibiotics should be based on the patient's symptoms, previous culture data, and institutional antibiograms. Ongoing therapy should be guided by culture and clinical data. Antimicrobial resistance is of great concern, particularly in this population, so careful attention to antibiotic selection and duration is needed.
- Published
- 2019
8. Modified Papanicolaou staining for oral swab samples stored long term
- Author
-
Vijaya Raj Bhatt, Alison G. Freifeld, Lepakshi S. V. Madduri, Srijayaprakash B. Uppada, Siddappa N. Byrareddy, Brooke Lawson, Sravani Singu, and Linda K. Bauer
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Histology ,Sample (material) ,Human immunodeficiency virus (HIV) ,Papanicolaou stain ,medicine.disease_cause ,Article ,Specimen Handling ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Humans ,Vaginal Smears ,030102 biochemistry & molecular biology ,Staining and Labeling ,business.industry ,Obstetrics ,General Medicine ,female genital diseases and pregnancy complications ,Term (time) ,Staining ,Medical Laboratory Technology ,030220 oncology & carcinogenesis ,Female ,business ,Limited resources ,Papanicolaou Test - Abstract
Pathologists collect swab samples for Papanicolaou (Pap) staining to diagnose various diseases including cancer and HIV. Time constraints and limited resources, may preclude staining a sample immediately. To re-confirm results, samples must be frozen for later analysis. We present a method for Pap staining cells that have been stored long term. An effective method for Pap staining of frozen cells should enable flexibility for processing samples.
- Published
- 2020
9. Contributors
- Author
-
James L. Abbruzzese, Omar Abdel-Wahab, Ghassan K. Abou-Alfa, Janet L. Abrahm, Jeffrey S. Abrams, Jeremy S. Abramson, Dara L. Aisner, Michelle Alonso-Basanta, Jesus Anampa, Megan E. Anderson, Emmanuel S. Antonarakis, Richard Aplenc, Frederick R. Appelbaum, Luiz H. Araujo, Ammar Asban, Edward Ashwood, Farrukh T. Awan, Juliet L. Aylward, Arjun V. Balar, Courtney J. Balentine, Stefan K. Barta, Nancy Bartlett, Karen Basen-Engquist, Lynda Kwon Beaupin, Ross S. Berkowitz, Donald A. Berry, Therese Bevers, John F. Boggess, Julie R. Brahmer, Janet Brown, Karen Brown, Powel Brown, Ilene Browner, Paul A. Bunn, William R. Burns, John C. Byrd, Karen Cadoo, David P. Carbone, H. Ballentine Carter, Jorge J. Castillo, Alfred E. Chang, Eric Chang, Stephen J. Chanock, Claudia I. Chapuy, Vikash P. Chauhan, Herbert Chen, Ronald C. Chen, Nai-Kong V. Cheung, Jennifer H. Choe, Michaele C. Christian, Paul M. Cinciripini, Michael F. Clarke, Robert E. Coleman, Robert L. Coleman, Adriana M. Coletta, Jerry M. Collins, Jean M. Connors, Michael Cools, Kevin R. Coombes, Jorge Cortes, Mauro W. Costa, Anne Covey, Kenneth H. Cowan, Christopher H. Crane, Jeffrey Crawford, Kristy Crooks, Daniel J. Culkin, Brian G. Czito, Piero Dalerba, Josep Dalmau, Mai Dang, Michael D'Angelica, Kurtis D. Davies, Myrtle Davis, Nicolas Dea, Ana De Jesus-Acosta, Angelo M. DeMarzo, Theodore L. DeWeese, Maximilian Diehn, Subba R. Digumarthy, Angela Dispenzieri, Khanh T. Do, Konstantin Dobrenkov, Jeffrey S. Dome, James H. Doroshow, Jay F. Dorsey, Marianne Dubard-Gault, Steven G. DuBois, Dan G. Duda, Malcolm Dunlop, Linda R. Duska, Madeleine Duvic, Imane El Dika, Hashem El-Serag, Jeffrey M. Engelmann, David S. Ettinger, Lola A. Fashoyin-Aje, Eric R. Fearon, James M. Ford, Wilbur A. Franklin, Phoebe E. Freer, Boris Freidlin, Alison G. Freifeld, Terence W. Friedlander, Debra L. Friedman, Arian F. Fuller, Lorenzo Galluzzi, Mark C. Gebhardt, Daniel J. George, Mark B. Geyer, Amato J. Giaccia, Mark R. Gilbert, Whitney Goldner, Donald P. Goldstein, Annekathryn Goodman, Karyn A. Goodman, Kathleen Gordon, Laura Graeff-Armas, Alexander J. Greenstein, Stuart A. Grossman, Stephan Grupp, Arjun Gupta, Irfanullah Haider, Missak Haigentz, John D. Hainsworth, Benjamin E. Haithcock, Christopher L. Hallemeier, Samir Hanash, Aphrothiti J. Hanrahan, James Harding, Michael R. Harrison, Muneer G. Hasham, Ernest Hawk, Jonathan Hayman, Jonathan E. Heinlen, N. Lynn Henry, Joseph Herman, Brian P. Hobbs, Ingunn Holen, Leora Horn, Neil S. Horowitz, Steven M. Horwitz, Odette Houghton, Scott C. Howard, Clifford A. Hudis, Stephen P. Hunger, Arti Hurria, David H. Ilson, Annie Im, Gopa Iyer, Elizabeth M. Jaffee, Reshma Jagsi, Rakesh K. Jain, William Jarnagin, Aminah Jatoi, Anuja Jhingran, David H. Johnson, Brian Johnston, Patrick G. Johnston, Kevin D. Judy, Lisa A. Kachnic, Orit Kaidar-Person, Sanjeeva Kalva, Deborah Y. Kamin, Hagop Kantarjian, Giorgos Karakousis, Maher Karam-Hage, Nadine M. Kaskas, Michael B. Kastan, Nora Katabi, Daniel R. Kaul, Scott R. Kelley, Nancy Kemeny, Erin E. Kent, Oliver Kepp, Simon Khagi, Joshua E. Kilgore, D. Nathan Kim, Bette K. Kleinschmidt-DeMasters, Edward L. Korn, Guido Kroemer, Geoffrey Y. Ku, Shivaani Kummar, Bonnie Ky, Daniel A. Laheru, Paul F. Lambert, Mark Lawler, Jennifer G. Le-Rademacher, John Y.K. Lee, Nancy Y. Lee, Susanna L. Lee, Jonathan E. Leeman, Andreas Linkermann, Jinsong Liu, Simon Lo, Jason W. Locasale, Charles L. Loprinzi, Maeve Lowery, Emmy Ludwig, Matthew A. Lunning, Robert A. Lustig, Mitchell Machtay, Crystal Mackall, David A. Mahvi, David M. Mahvi, Amit Maity, Neil Majithia, Marcos Malumbres, Karen Colbert Maresso, John D. Martin, Koji Matsuo, Natalie H. Matthews, Lauren Mauro, R. Samuel Mayer, Worta McCaskill-Stevens, Megan A. McNamara, Neha Mehta-Shah, Robert E. Merritt, Matthew I. Milowsky, Lori M. Minasian, Tara C. Mitchell, Demytra Mitsis, Michelle Mollica, Margaret Mooney, Farah Moustafa, Lida Nabati, Jarushka Naidoo, Amol Narang, Heidi Nelson, William G. Nelson, Suzanne Nesbit, Mark Niglas, Tracey O'Connor, Kenneth Offit, Mihaela Onciu, Eileen M. O’Reilly, Elaine A. Ostrander, Lisa Pappas-Taffer, Drew Pardoll, Jae H. Park, Anery Patel, Anish J. Patel, Steven R. Patierno, Steven Z. Pavletic, Peter C. Phillips, Miriam D. Post, Amy A. Pruitt, Christiane Querfeld, Vance A. Rabius, S. Vincent Rajkumar, Mohammad O. Ramadan, Erinn B. Rankin, Sushanth Reddy, Michael A. Reid, Scott Reznik, Tina Rizack, Jason D. Robinson, Leslie Robinson-Bostom, Carlos Rodriguez-Galindo, Paul B. Romesser, Steven T. Rosen, Myrna R. Rosenfeld, Nadia Rosenthal, Meredith Ross, Julia H. Rowland, Anthony H. Russell, Michael S. Sabel, Arjun Sahgal, Ryan D. Salinas, Erin E. Salo-Mullen, Manuel Salto-Tellez, Sydney M. Sanderson, John T. Sandlund, Victor M. Santana, Michelle Savage, Eric C. Schreiber, Lynn Schuchter, Liora Schultz, Michael V. Seiden, Morgan M. Sellers, Payal D. Shah, Jinru Shia, Konstantin Shilo, Eric Small, Angela B. Smith, Stephen N. Snow, David B. Solit, Anil K. Sood, Enrique Soto-Perez-de-Celis, Joseph A. Sparano, Vladimir S. Spiegelman, Sheri L. Spunt, Zsofia K. Stadler, David P. Steensma, Richard M. Stone, Steven Kent Stranne, Kelly Stratton, Bill Sugden, Andrew M. Swanson, Martin S. Tallman, James E. Talmadge, David T. Teachey, Catalina V. Teba, Ayalew Tefferi, Bin Tean Teh, Joyce M.C. Teng, Joel E. Tepper, Premal H. Thaker, Aaron P. Thrift, Arthur-Quan Tran, Grace Triska, Donald Trump, Kenneth Tsai, Chia-Lin Tseng, Diane Tseng, Sandra Van Schaeybroeck, Brian A. Van Tine, Erin R. Vanness, Gauri Varadhachary, Marileila Varella-Garcia, Richard L. Wahl, Michael F. Walsh, Thomas Wang, Jared Weiss, Irving L. Weissman, Shannon N. Westin, Jeffrey D. White, Richard Wilson, Richard J. Wong, Gary S. Wood, Yaohui G. Xu, Meng Xu-Welliver, Shlomit Yust-Katz, Timothy Zagar, Elaine M. Zeman, Tian Zhang, and James A. Zwiebel
- Published
- 2020
10. Infection in the Patient With Cancer
- Author
-
Alison G. Freifeld and Daniel R. Kaul
- Subjects
medicine.medical_specialty ,business.industry ,Risk of infection ,Cancer ,Neutropenia ,medicine.disease ,Transplantation ,Sepsis ,medicine ,In patient ,Stem cell ,business ,Intensive care medicine ,Complication - Abstract
Infection is a common complication of certain cancer treatments, particularly cytotoxic chemotherapies and stem cell transplantation which render patients neutropenic for various periods. In the absence of adequate neutrophils, bacterial infections may cause rapid onset of sepsis, typically heralded by the occurrence of fever. Accordingly, immediate administration of empiric antibiotic therapy is a standard approach to neutropenic patients who develop fever. Additionally, the presence of indwelling venous catheters, recent surgery or prolonged use of steroids and other immunosuppressant drugs can potentiate infections. Risk of infection varies significantly with underlying disease and those with hematologic malignancies are most prone to serious infectious complications including bacteremias, pneumonias and invasive fungal infections while those undergoing cycles of cytotoxic therapy for solid tumors are less commonly affected. Oncologists and other providers of cancer care must be familiar with the types of infections that can occur in patients with different cancers and therapies, and have a working knowledge of how to manage fever during neutropenia as swift and proper intervention may be life-saving for many patients.
- Published
- 2020
11. BK Viremia as a Predictor of Hemorrhagic Cystitis in Adults During the First 100 Days After Allogeneic Hematopoietic Stem Cell Transplantation
- Author
-
Jane L. Meza, Robert G. Bociek, L. F. Guzman Vinasco, Valerie Shostrom, V. Kesherwani, Alison G. Freifeld, Mohammad Awaji, and Catherine L Gebhart
- Subjects
Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,medicine.medical_treatment ,030106 microbiology ,Hemorrhage ,Viremia ,Hematopoietic stem cell transplantation ,030230 surgery ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Cystitis ,medicine ,Humans ,Transplantation, Homologous ,Retrospective Studies ,Polyomavirus Infections ,Transplantation ,business.industry ,Hematopoietic Stem Cell Transplantation ,Case-control study ,Retrospective cohort study ,Middle Aged ,Viral Load ,medicine.disease ,Control subjects ,Tumor Virus Infections ,BK Virus ,Case-Control Studies ,Female ,Surgery ,business ,Viral load ,Hemorrhagic cystitis - Abstract
In a retrospective case-control study, we aimed to assess the utility of plasma BK viral load value to predict hemorrhagic cystitis (HC) symptoms after allogeneic hematopoietic stem cell transplantation (alloHSCT). During first 100 post-transplantation days of all adult AlloHSCT recipients at the University of Nebraska Medical Center from October 1, 2011, to June 30, 2014, 8 unexcluded cases of HC were identified and matched with 88 unexcluded unaffected control cases. Viral loads were determined for archived DNA extracted from plasma collected within 3 weeks before transplantation until ∼100 days after transplantation. Clinical factors, time of onset of BK viremia, and BK viral load were compared between case and control subjects to identify risks for HC. Symptomatic HC occurred in 8/96 (8.3%) of patients at a median of 34 days after transplantation. BK viremia either before or during symptoms was detected in all 8 (100%) HC patients and in 20/88 (22.7%) of control subjects. BK viremia was detected at a median of 8 days before HC clinical symptoms. The log of first positive viral load was not a statistically significant predictor (P = .17) of symptomatic BK. Median BK viral load peak was significantly higher for 8 patients with HC versus 20 viremic patients without HC (6.66 vs 5.06; P .052). Further study is required to evaluate the predictive value of the BK viral load for HC.
- Published
- 2018
12. Clostridium difficile–Associated Diarrhea in the Oncology Patient
- Author
-
Kari Neemann and Alison G. Freifeld
- Subjects
Diarrhea ,Oncology ,medicine.medical_specialty ,Population ,Neutropenia ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Epidemiology ,medicine ,Humans ,030212 general & internal medicine ,education ,Adverse effect ,Intensive care medicine ,education.field_of_study ,Clostridioides difficile ,Oncology (nursing) ,business.industry ,Health Policy ,Clostridium difficile ,Antimicrobial ,medicine.disease ,030220 oncology & carcinogenesis ,medicine.symptom ,business - Abstract
Clostridium difficile is the most common cause of nosocomial diarrhea, resulting in significant morbidity and mortality in hospitalized patients. Oncology patients are particularly at risk of this infection secondary to frequent exposure to known risk factors. In a population in which diarrhea is a common adverse effect of chemotherapeutic regimens, diagnosis can be challenging secondary to current limitations in testing to differentiate between colonization and active infection. Although several currently available antimicrobial therapies achieve resolution of symptoms in this population, further research is needed to determine which agent least affects the host intestinal microbiota, especially in times of neutropenia and mucosal barrier injury. The purpose of this article is to review the current literature on the epidemiology, pathogenesis, and management of C difficile–associated diarrhea in the oncology population.
- Published
- 2017
13. Incidence of Febrile Neutropenia in Autologous Hematopoietic Stem Cell Transplant (HSCT) Recipients on levofloxacin prophylaxis
- Author
-
Alison G. Freifeld, Susanne Liewer, Valerie Shostrom, Andrea Zimmer, and Jessie Signorelli
- Subjects
Male ,medicine.medical_specialty ,Bacteremia ,Levofloxacin ,030230 surgery ,Transplantation, Autologous ,03 medical and health sciences ,0302 clinical medicine ,Chart review ,Internal medicine ,Medicine ,Humans ,Transplantation, Homologous ,Time to onset ,Febrile Neutropenia ,Retrospective Studies ,Transplantation ,business.industry ,Incidence (epidemiology) ,Incidence ,Hematopoietic Stem Cell Transplantation ,Hematopoietic stem cell ,Autologous hsct ,Antibiotic Prophylaxis ,Middle Aged ,medicine.disease ,Clostridium difficile infections ,Transplant Recipients ,Anti-Bacterial Agents ,Infectious Diseases ,medicine.anatomical_structure ,Clostridium Infections ,030211 gastroenterology & hepatology ,Female ,business ,Febrile neutropenia ,medicine.drug - Abstract
BACKGROUND Autologous hematopoietic stem cell transplant (HSCT) recipients are not uniformly considered as "high risk" enough to receive fluoroquinolone (FQ) prophylaxis. The risks versus benefits of FQ prophylaxis in autologous HSCT require further investigation. METHODS A retrospective chart review of patients > 19 years old who received an autologous HSCT at Nebraska Medicine analyzed two time periods (period 1: no prophylaxis [2013-2015] versus period 2: levofloxacin prophylaxis [2015-2016]) to characterize the clinical impact of levofloxacin prophylaxis on autologous HSCT recipients. RESULTS A total of 224 autologous HSCT were screened with 214 included. Febrile neutropenia (FN) developed in 101/113 (89%) versus 60/101 (59%) patients in the no prophylaxis (NPx) versus prophylaxis (Px) group (P
- Published
- 2019
14. Epidemiology, Diagnosis, Treatment, and Prevention of Influenza Infection in Oncology Patients
- Author
-
Razan El Ramahi and Alison G. Freifeld
- Subjects
medicine.medical_specialty ,Pneumonia, Viral ,Antiviral Agents ,Chemoprevention ,03 medical and health sciences ,Immunocompromised Host ,0302 clinical medicine ,Internal medicine ,Neoplasms ,Epidemiology ,Influenza, Human ,Medicine ,Humans ,In patient ,030212 general & internal medicine ,Letters to the Editor ,Pandemics ,Letter to the Editor ,Oncology (nursing) ,business.industry ,Health Policy ,Cancer ,medicine.disease ,Oncology ,Diagnosis treatment ,Hematological malignancy ,Influenza Vaccines ,030220 oncology & carcinogenesis ,Oncology patients ,Seasons ,business - Abstract
Influenza infection causes increased morbidity and higher mortality in patients receiving treatment of underlying cancer, particularly in those with hematological malignancy or patients who have undergone hematopoietic stem-cell transplantation. The illness is characterized by seasonality and nonspecific clinical manifestations of upper respiratory infection at a time when other respiratory illnesses are common in the community, making the diagnosis challenging. However, accurate and timely diagnosis by new molecular techniques is crucial in the management of immunocompromised patients, because delays in initiating appropriate therapy can have devastating consequences. Emergence of viral resistance to currently used antiviral agents is of concern, particularly in immunocompromised hosts, and warrants continued monitoring and surveillance. Early and effective treatment improves outcomes, but optimal therapeutic strategies in patients with cancer are not well defined. Health care and research efforts should focus on defining treatment guidelines in patients with cancer and attempt to improve on current vaccination strategies.
- Published
- 2019
15. Candida Infections in Hematopoietic and Solid Organ Transplant Recipients
- Author
-
Alison G. Freifeld and Carol A. Kauffman
- Subjects
Echinocandin ,Candida glabrata ,biology ,business.industry ,medicine.medical_treatment ,Mortality rate ,Mucous membrane ,Neutropenia ,medicine.disease ,biology.organism_classification ,medicine.anatomical_structure ,Immunology ,Medicine ,Disseminated disease ,business ,Candida albicans ,Central venous catheter ,medicine.drug - Abstract
Infections caused by Candida species range from local mucous membrane involvement to widely disseminated disease. In patients who have received a hematopoietic cell or solid organ transplant, candidiasis is one of the most common infections that is seen and is often life threatening. Candida species are part of the normal human microbiota and, as such, rarely cause infection in healthy hosts. Infections arise when the organisms are able to proliferate locally and gain access to the bloodstream from their normal mucosal or cutaneous colonization niche. Candidemia and invasive candidiasis are directly attributable to a breakdown of normal barriers, such as that which occurs with candidemia related to a central venous catheter, or to impairment of host defenses, which is especially prominent with neutropenia. The most common species to cause infection is Candida albicans, but increasingly, Candida glabrata is reported, especially among patients who have hematological malignancies or have received a transplant. Treatment has improved in the last several decades with the availability of multiple azole and echinocandin agents, all of which are less toxic than amphotericin B. However, crude mortality rates for patients with candidemia remain high, reflecting in part the very ill patients who develop this infection. Increasing evidence shows that the sooner antifungal treatment is initiated, the better the outcome; thus, in patients at high risk for invasive candidiasis, empirical treatment is appropriate while awaiting diagnostic test results. Prophylaxis, generally with an azole agent, is given routinely to recipients of a hematopoietic cell transplant and to certain high-risk solid organ transplant recipients.
- Published
- 2019
16. Prevention and Treatment of Cancer-Related Infections, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology
- Author
-
Randy Taplitz, Lindsey R. Baden, John W. Wilson, Alison G. Freifeld, Sankar Swaminathan, Shmuel Shoham, Karin G. Hoffmann, John N. Greene, Corey Casper, Brahm H. Segal, Ashley Morris Engemann, Jeffrey Topal, Daniel R. Kaul, Bernard C Camins, James I. Ito, Susan K. Seo, Gayle C. Blouin, Jose G. Montoya, Courtney Smith, Kenneth V. I. Rolston, Mark E. Lustberg, Erik R. Dubberke, Brenda W. Cooper, Gowri Satyanarayana, and Michael Angarone
- Subjects
0301 basic medicine ,Antifungal ,medicine.medical_specialty ,medicine.drug_class ,030106 microbiology ,Human immunodeficiency virus (HIV) ,medicine.disease_cause ,Communicable Diseases ,03 medical and health sciences ,0302 clinical medicine ,Neoplasms ,medicine ,Humans ,In patient ,Intensive care medicine ,medicine.diagnostic_test ,business.industry ,Cancer ,Hepatitis C ,Hepatitis B ,medicine.disease ,Clinical Practice ,Oncology ,Therapeutic drug monitoring ,030220 oncology & carcinogenesis ,Immunology ,business - Abstract
Infectious diseases are important causes of morbidity and mortality in patients with cancer. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prevention and Treatment of Cancer-Related Infections characterize the major pathogens to which patients with cancer are susceptible, with a focus on the prevention, diagnosis, and treatment of major common and opportunistic infections. This portion of the guidelines highlights the sections on antifungal and antiviral prophylaxis. Antifungal and antiviral prophylaxis recommendations have expanded over the past few years. New agents for the treatment of fungal infections and incorporation of therapeutic drug monitoring are presented. Antiviral prophylaxis for hepatitis B and management considerations for hepatitis C and HIV have been further developed.
- Published
- 2016
17. Causative Organisms and Associated Antimicrobial Resistance in Healthcare-Associated, Central Line–Associated Bloodstream Infections From Oncology Settings, 2009–2012
- Author
-
Isaac See, Alison G. Freifeld, and Shelley S. Magill
- Subjects
Adult ,0301 basic medicine ,Microbiology (medical) ,Oncology ,medicine.medical_specialty ,030106 microbiology ,Bacteremia ,Rate ratio ,medicine.disease_cause ,Article ,Immunocompromised Host ,03 medical and health sciences ,symbols.namesake ,0302 clinical medicine ,Antibiotic resistance ,Neoplasms ,Internal medicine ,Drug Resistance, Bacterial ,medicine ,Humans ,030212 general & internal medicine ,Poisson regression ,Cross Infection ,Central line ,Bacteria ,biology ,business.industry ,Pseudomonas aeruginosa ,biology.organism_classification ,Antimicrobial ,Confidence interval ,Infectious Diseases ,Catheter-Related Infections ,symbols ,business ,Enterococcus faecium - Abstract
BACKGROUND Recent antimicrobial resistance data are lacking from inpatient oncology settings to guide infection prophylaxis and treatment recommendations. We describe central line-associated bloodstream infection (CLABSI) pathogens and antimicrobial resistance patterns reported from oncology locations to the Centers for Disease Control and Prevention's National Healthcare Safety Network (NHSN). METHODS CLABSI data reported to NHSN from 2009 to 2012 from adult inpatient oncology locations were compared to data from nononcology adult locations within the same hospitals. Pathogen profile, antimicrobial resistance rates, and CLABSI incidence rates per 1000 central line-days were calculated. CLABSI incidence rates were compared using Poisson regression. RESULTS During 2009-2012, 4654 CLABSIs were reported to NHSN from 299 adult oncology units. The most common organisms causing CLABSI in oncology locations were coagulase-negative staphylococci (16.9%), Escherichia coli (11.8%), and Enterococcus faecium (11.4%). Fluoroquinolone resistance was more common among E. coli CLABSI in oncology than nononcology locations (56.5% vs 41.5% of isolates tested; P < .0001) and increased significantly from 2009-2010 to 2011-2012 (49.5% vs 60.4%; P = .01). Furthermore, rates of CLABSI were significantly higher in oncology compared to nononcology locations for fluoroquinolone-resistant E. coli (rate ratio, 7.37; 95% confidence interval [CI], 6.20-8.76) and vancomycin-resistant E. faecium (rate ratio, 2.27, 95% CI, 2.03-2.53). However, resistance rates for some organisms, such as Klebsiella species and Pseudomonas aeruginosa, were lower in oncology than in nononcology locations. CONCLUSIONS Antimicrobial-resistant E. coli and E. faecium have become significant pathogens in oncology. Practices for antimicrobial prophylaxis and empiric antimicrobial therapy should be regularly assessed in conjunction with contemporary antimicrobial resistance data.
- Published
- 2016
18. Nocardia arthritidis as a cause of disseminated nocardiosis in a patient with chronic lymphocytic leukemia
- Author
-
Peter C. Iwen, Alison G. Freifeld, Amity L. Roberts, and Rebecca M. Davidson
- Subjects
0301 basic medicine ,Chronic lymphocytic leukemia ,030106 microbiology ,Case Report ,Nocardia species ,Nocardia ,Microbiology ,03 medical and health sciences ,Nocardiosis ,medicine ,biology ,business.industry ,Nocardia arthritidis ,Disseminated nocardiosis ,Arthritidis ,medicine.disease ,biology.organism_classification ,bacterial infections and mycoses ,Infectious Diseases ,Rheumatoid arthritis ,Immunology ,Multilocus sequence typing ,bacteria ,business ,Disseminated - Abstract
A case of disseminated nocardiosis caused by Nocardia arthritidis in an immunocompromised patient with a history of chronic lymphocytic leukemia and rheumatoid arthritis is presented. This report highlights the use for multilocus sequence typing (MLST) in addition to single gene molecular sequencing to identify rare Nocardia species.
- Published
- 2016
- Full Text
- View/download PDF
19. 2666. De-escalation of Broad-Spectrum Antibiotics in Hematopoietic Stem Cell Transplant Patients During Initial Episode of Febrile Neutropenia
- Author
-
Alison G. Freifeld, Lindsey Rearigh, Andrea Zimmer, and Erica J Stohs
- Subjects
medicine.medical_specialty ,business.industry ,Hematopoietic stem cell ,medicine.disease ,Abstracts ,Broad spectrum ,Infectious Diseases ,medicine.anatomical_structure ,Oncology ,Internal medicine ,Poster Abstracts ,medicine ,Transplant patient ,business ,De-escalation ,Febrile neutropenia - Abstract
Background Febrile neutropenia (FN) is a common and serious complication in patients undergoing hematopoietic stem cell transplant (HSCT). Typically, broad-spectrum antibiotics (BSA) are promptly initiated with controversy on timing of de-escalation. ECIL 2013 guidelines suggest de-escalation after 72 hours if the patient is infection free and afebrile for at least 48 hours. Conversely, the 2011 IDSA recommends continuing BSA in patients who defervesce until absolute neutrophil count (ANC) recovery. In 2014, our center’s practice changed to early de-escalation and we sought to compare outcomes between the two practices. Methods We retrospectively analyzed patients who underwent a HSCT in 2013 and 2017 with an episode of FN and negative infectious work up. The standard care group (SCG) were continued on BSA until ANC recovery. The early de-escalation group (EDG) de-escalated to fluoroquinolone prophylaxis at least 24 hours prior to ANC recovery after the patient was fever free for 48 hours. The primary end-point was duration of BSA. Secondary endpoints included 30-day mortality, re-hospitalization and length of stay (LOS) from FN. Median values were compared with the Mann–Whitney test. Results Among 229 HSCT patients, 155 (68%) developed FN post-transplant and of those 97 (63%) were without infection (13 EDG and 84 SCG). Initial FN duration of BSA was less in the EDG (3.09 days vs. 4.69 days, P = 0.069). Total antibiotic free days to 30 day follow-up were similar (EDG 24.08 vs SCG 25.19, P = 0.81). Duration of neutropenia was less in the SCG with 7.99 days compared with 11.69 days in the EDG (P = 0.007), but duration of initial fever was less in the EDG (2.55 days vs. 3.33 days, P = 0.023). 30 day mortality was 0% in both groups. Rates of re-hospitalization within 30 days were approximately the same (7.1% vs. 7.6%). LOS from FN was not significantly different with 6.68 days in SCG and 7.75 days in EDG (P = 0.140). More new bacterial infections were identified within 30 days of FN in the SCG than the EDG (10.7% vs. 7.6%). Conclusion Early BSA de-escalation resulted in no significant difference in LOS from FN and fewer days of BSA with 30-day mortality and re-hospitalization rates similar. This data suggest de-escalating BSA prior to ANC recovery is likely safe and leads to less BSA exposure, but more multi-center data are needed. Disclosures All authors: No reported disclosures.
- Published
- 2019
20. Clostridium difficile stool shedding in infants hospitalized in two neonatal intensive care units is lower than previous point prevalence estimates using molecular diagnostic methods
- Author
-
Xing Zhao, Andrea Green Hines, Lynne D. Willett, Peter C. Iwen, Ann L. Anderson Berry, Kari A. Simonsen, and Alison G. Freifeld
- Subjects
medicine.medical_specialty ,Epidemiology ,Bacterial Toxins ,Loop-mediated isothermal amplification ,Prevalence ,Clostridium difficile toxin A ,Patient characteristics ,Gastroenterology ,Feces ,03 medical and health sciences ,0302 clinical medicine ,Bacterial Proteins ,Intensive Care Units, Neonatal ,Internal medicine ,Intensive care ,medicine ,Humans ,030212 general & internal medicine ,Bacteriological Techniques ,Genes, Essential ,Molecular epidemiology ,Clostridioides difficile ,business.industry ,Incidence (epidemiology) ,lcsh:RJ1-570 ,Infant ,lcsh:Pediatrics ,Clostridium difficile ,United States ,Pediatrics, Perinatology and Child Health ,Clostridium Infections ,030211 gastroenterology & hepatology ,business ,Multiplex Polymerase Chain Reaction ,Research Article ,Triose-Phosphate Isomerase - Abstract
Background The point prevalence of Clostridium difficile stool shedding in hospitalized infants from two neonatal intensive care units (NICUs) was examined utilizing standard clinical testing compared with duplex PCR to identify toxigenic and non-toxigenic C. difficile strains. Methods All infants from the two NICUs affiliated with a single academic medical center were eligible for inclusion. Stool collection was blinded to patient characteristics and occurred during a one week period at each NICU and repeated with a second weeklong collection 6 months later to increase sample size. Stools were tested for C. difficile using EIA (GDH/toxin A/B) with samples testing +/+ or +/− subsequently evaluated by Loop-Mediated Isothermal Amplification (LAMP) and by duplex PCR amplification of tcdB and tpi (housekeeping) genes. Cytotoxicity assays were performed on all samples positive for C. difficile by any modality. Results Eighty-four stools were collected from unique infants for evaluation. EIA results showed 6+/+ [7.1%], 7 +/− [8.3%], and 71 −/− [84.5%] samples. All 6 EIA +/+ were confirmed as toxigenic C. difficile by LAMP; 6/7 EIA +/− were negative by LAMP with one identified as invalid. Duplex PCR concurred with LAMP in all 6 stools positive for toxigenic C. difficile. PCR identified 2 EIA −/− stools positive for tpi, indicating shedding of non-toxigenic C. difficile. Cytotoxicity assay was positive in 4/6 duplex PCR positive samples and negative for all stools that were EIA +/− but negative by molecular testing. Conclusions C. difficile blinded point prevalence in infants from two NICUs was 7.1% by molecular methods; and lower than expected based on historical incidence estimates. In house duplex PCR had excellent concordance with clinically available LAMP and EIA tests, and added detection of non-toxigenic C. difficile strain shedding. Evolving NICU care practices may be influencing the composition of infant gut microbiota and reducing the point prevalence of C. difficile shedding in NICU patient stools.
- Published
- 2018
21. Infections in Cancer
- Author
-
Alison G. Freifeld and Andrea Zimmer
- Subjects
Oncology ,medicine.medical_specialty ,Chemotherapy ,business.industry ,medicine.medical_treatment ,Internal medicine ,Bacteremia ,medicine ,Cancer ,business ,medicine.disease ,Febrile neutropenia ,Cancer treatment - Published
- 2018
22. 1016. Bloodstream Infection Survey in High-Risk Oncology Patients (BISHOP) With Fever and Neutropenia (FN): Predictors for Morbidity and Mortality
- Author
-
Pranatharthi H. Chandrasekar, John W. Baddley, Thomas J. Walsh, Jane L. Meza, Yuning Zhang, Randy Taplitz, Alison G. Freifeld, Christopher Arnold, Zeinab El Boghdadly, Jose G. Montoya, Steven A. Pergam, Andrea Zimmer, Eileen K Maziarz, Jo Anne H. Young, Lynne Strasfeld, Gowri Satyanarayana, Kenneth V. I. Rolston, and Shmuel Shoham
- Subjects
medicine.medical_specialty ,business.industry ,education ,Neutropenia ,medicine.disease ,Abstracts ,Infectious Diseases ,Oncology ,B. Poster Abstracts ,Internal medicine ,Bloodstream infection ,medicine ,Oncology patients ,business - Abstract
Background Blood stream infection (BSI) during neutropenia is associated with high risk for morbidity and mortality in patients with hematologic malignancies receiving chemotherapy or undergoing hematopoietic cell transplant (HCT). We sought to identify factors associated with increased risk for critical illness (CI) morbidities within 7 days of BSI with index FN following chemotherapy. Methods A prospective ongoing survey among 14 high-volume US cancer centers submitting clinical and microbiologic data from consecutive HM patients with blood stream infection (BSI) during first FN after cytotoxic chemotherapy or HCT. We evaluated factors influencing poor outcomes defined as critical illness (need for pressor support, mechanical ventilation, new pneumonia or new BSI) within 7 days of BSI with index FN. Concordance between antibiotic and BSI isolate was determined by investigator (AZ, AF) interpretation of susceptibility reports provided by each center compared with the initial antimicrobial regimen (IAR) used, for single organism bacteremias only. Results Among 294 FN bacteremic episodes (93 HCT) were 336 bacterial pathogens (48.5% Gram-negative [GN], 46.5% Gram-positive [GP], and 6% anaerobes). Death occurred in 11/294 (4%) and 41/294 (14%) had CI by day 8. At FN presentation, mean MASCC score of those with CI vs. those without was 16.9 vs. 18.6 (P = 0.03) and there was a trend toward higher mean PITT scores for patients with CI by day 8 vs. those without (1.54 vs. 0.82 (P = 0.08)). Among GN bacteremias, 15% developed CI vs. 14.5% in nonviridans group Streptococci (VGS) GP bacteremias, and 10.9% in VGS bacteremias (NS). Among patients with single organism bacteremias (88% of all BSI), mismatch of IAR coverage with isolate susceptibilities occurred in 16.7% (38/227). Among patients whom IAR was active vs. inactive against BSI isolate, 16% vs 14.3%, respectively, developed CI (P = 0.81). Conclusion These data indicate that the MASCC score applied to high-risk inpatients may be a predictor for CI in the first week after bacteremia FN. The PITT shows less correlation with poor outcomes. There was no association between isolate type (GN, GP, or VGS) and CI. Notably there was no association between mismatched BSI susceptibility and antimicrobial spectrum of the IAR and early CI. Disclosures A. G. Freifeld, Merck: Investigator, Research grant. A. Zimmer, Merck: Investigator, Research grant. S. Pergam, Merck: Consultant, Consulting fee. Chimerix: Consultant, Consulting fee. K. V. Rolston, Merck: Investigator, Research grant. JMI Laboratories: Investigator, Research grant. Shionogi (Japan): Investigator, Research grant. S. Shoham, Merck: Investigator and Scientific Advisor, Consulting fee and Grant recipient. Astellas: Investigator, Grant recipient. Shionogi (Japan): Investigator, Grant recipient. Gilead: Investigator, Grant recipient. Shire: Investigator, Grant recipient. T. J. Walsh, Merck: Grant Investigator, Research grant. Atellas: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Research grant. Gilead: Scientific Advisor, Consulting fee. Allergan: Grant Investigator and Scientific Advisor, Consulting fee and Research grant. Scynexis: Grant Investigator, Research grant. Amplyx: Grant Investigator, Research grant. Shionogi: Scientific Advisor, Consulting fee. J. A. Young, GSK: Investigator, The University of Minnesota is reimbursed for contract costs associated with conducting clinical trials of vaccine. I receive no personal financial benefit. Y. Zhang, Merck: Investigator, Research grant. J. Meza, Merck: Investigator, Research grant.
- Published
- 2018
23. Histoplasmosis Complicating Tumor Necrosis Factor–α Blocker Therapy: A Retrospective Analysis of 98 Cases
- Author
-
Cynthia A. Hoey, David R. Andes, Chadi A. Hage, Jennifer L. Dotson, L. Joseph Wheat, David S. McKinsey, Rachel Miller, Steven D. Burdette, D. Kaul, Smyrna Abou Antoun, Kassem A. Hamoud, Maha A. Assi, Mary E. Money, William E. Muth, Alison G. Freifeld, Paschalis Vergidis, Frederick T. Steiner, Randall C. Walker, Thein Myint, David E. Liebers, Vidhya Prakash, Robin K. Avery, and Jana Dickter
- Subjects
Adult ,Male ,Microbiology (medical) ,medicine.medical_specialty ,Antifungal Agents ,Adolescent ,Anti-Inflammatory Agents ,Gastroenterology ,Histoplasmosis ,Etanercept ,Arthritis, Rheumatoid ,Young Adult ,Pharmacotherapy ,Immune Reconstitution Inflammatory Syndrome ,Recurrence ,Internal medicine ,Adalimumab ,Humans ,Medicine ,Child ,Articles and Commentaries ,Aged ,Retrospective Studies ,Aged, 80 and over ,Tumor Necrosis Factor-alpha ,business.industry ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Infliximab ,Discontinuation ,Surgery ,Treatment Outcome ,Infectious Diseases ,Concomitant ,Female ,business ,medicine.drug - Abstract
Background. Histoplasmosis may complicate tumor necrosis factor (TNF)–α blocker therapy. Published case series provide limited guidance on disease management. We sought to determine the need for long-term antifungal therapy and the safety of resuming TNF-α blocker therapy after successful treatment of histoplasmosis. Methods. We conducted a multicenter retrospective review of 98 patients diagnosed with histoplasmosis between January 2000 and June 2011. Multivariate logistic regression was used to evaluate risk factors for severe disease. Results. The most commonly used biologic agent was infliximab (67.3%). Concomitant corticosteroid use (odds ratio [OR], 3.94 [95% confidence interval {CI}, 1.06–14.60]) and higher urine Histoplasma antigen levels (OR, 1.14 [95% CI, 1.03–1.25]) were found to be independent predictors of severe disease. Forty-six (47.4%) patients were initially treated with an amphotericin B formulation for a median duration of 2 weeks. Azole treatment was given for a median of 12 months. TNF-α blocker therapy was initially discontinued in 95 of 98 (96.9%) patients and later resumed in 25 of 74 (33.8%) patients at a median of 12 months (range, 1–69 months). The recurrence rate was 3.2% at a median follow-up period of 32 months. Of the 3 patients with recurrence, 2 had restarted TNF-α blocker therapy, 1 of whom died. Mortality rate was 3.2%. Conclusions. In this study, disease outcomes were generally favorable. Discontinuation of antifungal treatment after clinical response and an appropriate duration of therapy, probably at least 12 months, appears safe if pharmacologic immunosuppression has been held. Resumption of TNF-α blocker therapy also appears safe, assuming that the initial antifungal therapy was administered for 12 months.
- Published
- 2015
24. Efficacy of β-Lactam/β-Lactamase Inhibitor Combinations for the Treatment of Bloodstream Infection Due to Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae in Hematological Patients with Neutropenia
- Author
-
F. Herrera, Jordi Carratalà, Guillermo Maestro de la Calle, Cristina Royo-Cebrecos, Carlos Cervera, Murat Akova, Maddalena Peghin, Georg Maschmeyer, Pilar Martín-Dávila, Mercè Gurguí, Jesús Rodríguez-Baño, Isabel Ruiz-Camps, Angela Cano, Yolanda Meije, Adriana Manzur, Teresa C. Sukiennik, Edson Abdala, Wanessa Trindade Clemente, Alison G. Freifeld, Cristian Tebe, Miguel Montejo, Thomas Gottlieb, Lucía Gómez, Carlota Gudiol, R. Alvarez, European Society of Clinical Microbiology and Infectious Diseases, Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, European Commission, Red Española de Investigación en Patología Infecciosa, [Gudiol, Carlota] Univ Barcelona, Bellvitge Univ Hosp, IDIBELL, Infect Dis Dept, Barcelona, Spain, [Royo-Cebrecos, Cristina] Univ Barcelona, Bellvitge Univ Hosp, IDIBELL, Infect Dis Dept, Barcelona, Spain, [Carratala, Jordi] Univ Barcelona, Bellvitge Univ Hosp, IDIBELL, Infect Dis Dept, Barcelona, Spain, [Gudiol, Carlota] Duran & Reynals Hosp, ICO, Barcelona, Spain, [Abdala, Edson] Univ Sao Paulo, Fac Med, Inst Canc Estado Sao Paulo, Sao Paulo, Brazil, [Akova, Murat] Hacettepe Univ, Sch Med, Ankara, Turkey, [Alvarez, Rocio] Univ Seville, CSIC, Univ Hosp Virgen Rocio & Virgen Macarena, Inst Biomed Seville IBiS,Infect Dis Res Grp,Clin, Seville, Spain, [Maestro-de la Calle, Guillermo] Univ Complutense, Sch Med, Octubre Univ Hosp 12, Inst Invest Hosp Octubre 12 i 12,Infect Dis Unit, Madrid, Spain, [Cano, Angela] UCO, Reina Sofia Univ Hosp, IMIBIC, Cordoba, Spain, [Cervera, Carlos] Univ Alberta Hosp, Edmonton, AB, Canada, [Clemente, Wanessa T.] Univ Fed Minas Gerais, Hosp Clin, Digest Transplant Serv, Belo Horizonte, MG, Brazil, [Martin-Davila, Pilar] Hosp Ramon & Cajal, Infect Dis Dept, Madrid, Spain, [Freifeld, Alison] Univ Nebraska, Med Ctr, Internal Med Infect Dis Sect, Omaha, NE 68182 USA, [Gomez, Lucia] Univ Hosp Mutua Terrassa, Internal Med, Barcelona, Spain, [Gottlieb, Thomas] Concord Hosp, Dept Microbiol & Infect Dis, Concord, NSW, Australia, [Gurgui, Merce] Univ Autonoma Barcelona, Hosp Santa Creu & Sant Pau, Infect Dis Unit, Barcelona, Spain, [Gurgui, Merce] Univ Autonoma Barcelona, Inst Invest Biomed Sant Pau, Barcelona, Spain, [Herrera, Fabian] CEMIC, Dept Med, Infect Dis Sect, Buenos Aires, DF, Argentina, [Manzur, Adriana] Hosp Rawson, Infect Dis, San Juan, Argentina, [Maschmeyer, Georg] Charite, Med Sch, Acad Teaching Hosp, Dept Hematol Oncol & Palliat Care,Klinikum Ernst, Berlin, Germany, [Meije, Yolanda] Barcelona Hosp, SCIAS, Internal Med Dept, Infect Dis Unit, Barcelona, Spain, [Montejo, Miguel] Cruces Univ Hosp, Infect Dis Unit, Bilbao, Spain, [Peghin, Maddalena] Santa Maria Misericordia Univ Hosp, Infect Dis Div, Udine, Italy, [Rodriguez-Bano, Jesus] Univ Seville, Univ Hosp Virgen Macarena & Virgen Rocio IBiS, Dept Med, Clin Unit Infect Dis Microbiol & Prevent Med, Seville, Spain, [Ruiz-Camps, Isabel] Vall Hebron Univ Hosp, Infect Dis Dept, Barcelona, Spain, [Sukiennik, Teresa C.] Hosp Santa Casa Misericordia Porto Alegre, Porto Alegre, RS, Brazil, [Tebe, Cristian] Rovira & Virgili Univ, Inst Biomed Res Bellvitge, Stat Advisory Serv, Tarragona, Spain, [Gudiol, Carlota] Inst Salud Carlos III, REIPI Spanish Network Res Infect Dis, Madrid, Spain, [Royo-Cebrecos, Cristina] Inst Salud Carlos III, REIPI Spanish Network Res Infect Dis, Madrid, Spain, [Meije, Yolanda] Inst Salud Carlos III, REIPI Spanish Network Res Infect Dis, Madrid, Spain, [Montejo, Miguel] Inst Salud Carlos III, REIPI Spanish Network Res Infect Dis, Madrid, Spain, [Rodriguez-Bano, Jesus] Inst Salud Carlos III, REIPI Spanish Network Res Infect Dis, Madrid, Spain, [Ruiz-Camps, Isabel] Inst Salud Carlos III, REIPI Spanish Network Res Infect Dis, Madrid, Spain, [Carratala, Jordi] Inst Salud Carlos III, REIPI Spanish Network Res Infect Dis, Madrid, Spain, ESGBIS, ESGICH, Ministerio de Economia y Competitividad, Instituto de Salud Carlos III - European Development Regional Fund 'A way to achieve Europe' EDRF, Spanish Network for the Research in Infectious Diseases, COMBACTE-NET, COMBACTE-CARE, COMBACTE-MAGNET, Innovative Medicines Initiative (European Union), Innovative Medicines Initiative (EFPIA), Merck, Astellas, Novartis, Pfizer, MSD, Janssen, Astra-Zeneca, and İç Hastalıkları
- Subjects
0301 basic medicine ,Male ,Definitive Therapy ,Bacteremia ,Escherichia-coli ,Cohort Studies ,chemistry.chemical_compound ,Bloodstream infection ,Case fatality rate ,polycyclic compounds ,beta-lactam/beta-lactamase inhibitors ,Pharmacology (medical) ,Pharmacology & Pharmacy ,Cancer ,biology ,Klebsiella-pneumoniae ,Enterobacteriaceae Infections ,Middle Aged ,Enterobacteriaceae ,Anti-Bacterial Agents ,Risk-factors ,Infectious Diseases ,Beta-lactam/beta-lactamase inhibitors ,Cohort ,Lactam ,Female ,beta-Lactamase Inhibitors ,Adult ,medicine.medical_specialty ,Neutropenia ,030106 microbiology ,bloodstream infection ,Outcomes ,Clinical Therapeutics ,beta-Lactams ,Microbiology ,beta-Lactamases ,03 medical and health sciences ,β lactamase inhibitor ,Piperacillin-tazobactam ,Internal medicine ,medicine ,Humans ,Mortality ,Intensive care medicine ,Pharmacology ,business.industry ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,biology.organism_classification ,bacterial infections and mycoses ,mortality ,chemistry ,ESBLs ,Carbapenems ,bacteria ,Therapy ,Bloodstream infections ,business - Abstract
β-Lactam/β-lactamase inhibitors (BLBLIs) were compared to carbapenems in two cohorts of hematological neutropenic patients with extended-spectrum-β-lactamase (ESBL) bloodstream infection (BSI): the empirical therapy cohort (174 patients) and the definitive therapy cohort (251 patients). The 30-day case fatality rates and other secondary outcomes were similar in the two therapy groups of the two cohorts and also in the propensity-matched cohorts. BLBLIs might be carbapenem-sparing alternatives for the treatment of BSI due to ESBLs in these patients., We thank the ESGBIS and the ESGICH study groups for supporting the study. This study was supported by Ministerio de Economía y Competitividad, Instituto de Salud Carlos III—cofinanced by European Development Regional Fund “A way to achieve Europe” EDRF, Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015).
- Published
- 2017
25. Endemic fungal infections in solid organ and hematopoietic cell transplant recipients enrolled in the Transplant-Associated Infection Surveillance Network (TRANSNET)
- Author
-
Carol A. Kauffman, Kaitlin Benedict, Elias Anaissie, Mindy G. Schuster, Benjamin Park, Kieren A. Marr, Alison G. Freifeld, Vicki A. Morrison, Tom Chiller, Loreen A. Herwaldt, Peter G. Pappas, John W. Baddley, Barbara D. Alexander, R. C. Walker, Thomas F. Patterson, Katherine M. Knapp, David R. Andes, G. M. Lyon, and James I. Ito
- Subjects
Adult ,Male ,medicine.medical_specialty ,Antifungal Agents ,Time Factors ,Adolescent ,Endemic Diseases ,medicine.medical_treatment ,Comorbidity ,Hematopoietic stem cell transplantation ,Blastomycosis ,Article ,Organ transplantation ,Histoplasmosis ,Young Adult ,Amphotericin B ,Internal medicine ,medicine ,Humans ,Cumulative incidence ,Prospective Studies ,Child ,Respiratory Tract Infections ,Aged ,Transplantation ,Coccidioidomycosis ,Respiratory tract infections ,Coinfection ,business.industry ,Incidence ,Hematopoietic Stem Cell Transplantation ,Organ Transplantation ,Middle Aged ,medicine.disease ,United States ,surgical procedures, operative ,Infectious Diseases ,Immunology ,Female ,Itraconazole ,business - Abstract
Background Invasive fungal infections are a major cause of morbidity and mortality among solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients, but few data have been reported on the epidemiology of endemic fungal infections in these populations. Methods Fifteen institutions belonging to the Transplant-Associated Infection Surveillance Network prospectively enrolled SOT and HCT recipients with histoplasmosis, blastomycosis, or coccidioidomycosis occurring between March 2001 and March 2006. Results A total of 70 patients (64 SOT recipients and 6 HCT recipients) had infection with an endemic mycosis, including 52 with histoplasmosis, 9 with blastomycosis, and 9 with coccidioidomycosis. The 12-month cumulative incidence rate among SOT recipients for histoplasmosis was 0.102%. Occurrence of infection was bimodal; 28 (40%) infections occurred in the first 6 months post transplantation, and 24 (34%) occurred between 2 and 11 years post transplantation. Three patients were documented to have acquired infection from the donor organ. Seven SOT recipients with histoplasmosis and 3 with coccidioidomycosis died (16%); no HCT recipient died. Conclusions This 5-year multicenter prospective surveillance study found that endemic mycoses occur uncommonly in SOT and HCT recipients, and that the period at risk extends for years after transplantation.
- Published
- 2014
26. MSG-01: A Randomized, Double-Blind, Placebo-Controlled Trial of Caspofungin Prophylaxis Followed by Preemptive Therapy for Invasive Candidiasis in High-Risk Adults in the Critical Care Setting
- Author
-
Juan Pablo Caeiro, William E. Dismukes, Annette C. Reboli, Roger Bedimo, Sanjay G. Revankar, Shmuel Shoham, Jose A. Vazquez, Alison G. Freifeld, Minh Hong Nguyen, Craig A. Wood, Andrew O. Westfall, Jeanna Beth Deerman, Robert F. Betts, Carol A. Kauffman, Mindy G. Schuster, Peter G. Pappas, Julie E. Mangino, Jack D. Sobel, David M. Mushatt, Luis Ostrosky-Zeichner, Marc A. Judson, and Michelle A. Barron
- Subjects
Adult ,Male ,Microbiology (medical) ,medicine.medical_specialty ,Antifungal Agents ,Placebo-controlled study ,Placebo ,law.invention ,Echinocandins ,Lipopeptides ,chemistry.chemical_compound ,Double-Blind Method ,Caspofungin ,Risk Factors ,law ,Internal medicine ,Clinical endpoint ,Humans ,Medicine ,Candidiasis, Invasive ,Risk factor ,Aged ,business.industry ,Surrogate endpoint ,Incidence ,Middle Aged ,Intensive care unit ,Clinical trial ,Intensive Care Units ,Treatment Outcome ,Infectious Diseases ,chemistry ,Anesthesia ,Female ,Pre-Exposure Prophylaxis ,business - Abstract
Background Invasive candidiasis is the third most common bloodstream infection in the intensive care unit (ICU) and is associated with morbidity and mortality. Prophylaxis and preemptive therapy are attractive strategies for this setting. Methods We conducted a multicenter, randomized, double-blind, placebo-controlled trial of caspofungin as antifungal prophylaxis in 222 adults who were in the ICU for at least 3 days, were ventilated, received antibiotics, had a central line, and had 1 additional risk factor (parenteral nutrition, dialysis, surgery, pancreatitis, systemic steroids, or other immunosuppressants). Subjects' (1,3)-β-d-glucan levels were monitored twice weekly. The primary endpoint was the incidence of proven or probable invasive candidiasis by EORTC/MSG criteria in patients who did not have disease at baseline. Patients who had invasive candidiasis were allowed to break the blind and receive preemptive therapy with caspofungin. The preemptive approach analysis included patients all patients who received study drug, including those positive at baseline. Results The incidence of proven/probable invasive candidiasis in the placebo and caspofungin arms was 16.7% (14/84) and 9.8% (10/102), respectively, for prophylaxis (P = .14), and 30.4% (31/102) and 18.8% (22/117), respectively, for the preemptive approach (P = .04); however, this analysis included patients with baseline disease. There were no significant differences in the secondary endpoints of mortality, antifungal use, or length of stay. There were no safety differences. Conclusions Caspofungin was safe and tended to reduce the incidence of invasive candidiasis when used for prophylaxis, but the difference was not statistically significant. A preemptive therapy approach deserves further study. Clinical trials registration NCT00520234.
- Published
- 2014
27. 1585. Bloodstream Infection Survey in High-Risk Oncology Patients (BISHOP) with Fever and Neutropenia (FN): Correlation Between Initial Empiric Antibiotic Regimen Correlation and Susceptibility Patterns
- Author
-
Shmuel Shoham, Randy Taplitz, Eileen K Maziarz, Jo Anne H. Young, Alison G. Freifeld, Andrea Zimmer, Carlos A. Gomez, Steven A. Pergam, Pranatharthi H. Chandrasekar, Bishop, Lynne Strasfeld, Gowri Satyanarayana, Christopher Arnold, Kenneth V. I. Rolston, Zeinab El Boghdadly, John W. Baddley, Yuning Zhang, Jane L. Meza, and Thomas J. Walsh
- Subjects
medicine.medical_specialty ,Antibiotic regimen ,business.industry ,education ,Neutropenia ,medicine.disease ,Abstracts ,Infectious Diseases ,B. Poster Abstracts ,Oncology ,Internal medicine ,Bloodstream infection ,medicine ,Oncology patients ,business ,health care economics and organizations - Abstract
Background The empiric initial antibiotic regimen (IAR) for treatment of febrile neutropenia (FN) relies on a knowledge of epidemiology and susceptibility patterns of bacterial bloodstream infections (BSI), especially in high-risk patient populations, i.e., those receiving chemotherapy for hematologic malignancies (HM) or undergoing hematopoietic stem cell transplant (HCT). As the last US national survey of BSI epidemiology in cancer patients was published in 2003, we sought to update these data focusing exclusively on high-risk patients with attention to IARs used and their concordance with susceptibilities of isolated bloodstream pathogens. Methods A prospective ongoing survey among 14 high-volume US cancer centers submitting clinical and microbiologic data from consecutive HM patients with BSI during first FN after cytotoxic chemotherapy or HCT. Concordance between antibiotic and BSI was determined by investigator (AZ, AF) interpretation of susceptibility reports provided by each center compared with IAR used, for single organism bacteremias only. Results Among 294 FN bacteremic episodes (93 HCT), there were 336 bacterial pathogens (48.5% Gram negative [GN] 46.5% Gram positive [GP] and 6% anaerobes), with 88% monomicrobial episodes. E. coli and viridans group Streptococci (VGS) were the most commonly isolated GN and GP, respectively, each accounting for nearly 25% of total organisms identified. IARs included cefepime 61%, piperacillin–tazobactam 24%, and meropenem 8%. Isolates were nonsusceptible to the IAR in 38/227 (17%) of FN episodes. Antibiotic mismatch was more likely to occur with a non-VGS GP (37%) vs. GN (13%) or VGS (2%) P < 0.001. Conclusion This is the first US national survey of high-risk BSI in FN. Although mismatch between BSI and IAR occurs in 17% of FN bacteremia episodes, this is driven primarily by non-VGS GP isolates such as CoNS and MRSA. Currently used IARs, comprised primarily of cefepime and piperacillin–tazobactam, generally provide reliable coverage for GN isolates across the United States (87%) but careful tracking of this rate is essential to identify further erosion of coverage in the current era of antimicrobial resistance. Disclosures A. Zimmer, Merck: Investigator, Research grant. A. G. Freifeld, Merck: Investigator, Research grant. S. Pergam, Merck: Consultant, Consulting fee; Chimerix: Consultant, Consulting fee. K. V. Rolston, Merck: Investigator, Research grant; JMI Laboratories: Investigator, Research grant; Shionogi (Japan): Investigator, Research grant. S. Shoham, Merck: Investigator and Scientific Advisor, Consulting fee and Grant recipient; Astellas: Investigator, Grant recipient; Shionogi (Japan): Investigator, Grant recipient; Gilead: Investigator, Grant recipient; Shire: Investigator, Grant recipient. T. J. Walsh, Merck: Grant Investigator, Research grant; Atellas: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Research grant; Gilead: Scientific Advisor, Consulting fee; Allergan: Grant Investigator and Scientific Advisor, Consulting fee and Research grant; Scynexis: Grant Investigator, Research grant; Amplyx: Grant Investigator, Research grant; Shionogi: Scientific Advisor, Consulting fee. J. A. Young, GSK: Investigator, The University of Minnesota is reimbursed for contract costs associated with conducting clinical trials of vaccine. I receive no personal financial benefit.. J. Meza, Merck: Investigator, Research grant. Y. Zhang, Merck: Investigator, Research grant.
- Published
- 2018
28. Prevention and Treatment of Cancer-Related Infections
- Author
-
Ashley Morris-Engemann, Sankar Swaminathan, James I. Ito, John P. Greer, Brahm H. Segal, Emily R. Mackler, Peter G. Pappas, Michael Angarone, Dorothy A. Shead, Kieren A. Marr, Judith E. Karp, Erik R. Dubberke, Earl King, William Bensinger, Corey Casper, Kenneth V. I. Rolston, Alison G. Freifeld, Susan K. Seo, Ramiro Garzon, Lindsey R. Baden, Maoko Naganuma, John N. Greene, Daniel R. Kaul, and Jose G. Montoya
- Subjects
medicine.medical_specialty ,Antifungal Agents ,Neutropenia ,medicine.medical_treatment ,MEDLINE ,Antineoplastic Agents ,Disease ,Hematopoietic stem cell transplantation ,Antiviral Agents ,Immunocompromised Host ,Risk Factors ,Neoplasms ,medicine ,Humans ,Antibiotic prophylaxis ,Intensive care medicine ,business.industry ,Hematopoietic Stem Cell Transplantation ,Cancer ,Bacterial Infections ,medicine.disease ,Anti-Bacterial Agents ,Increased risk ,Mycoses ,Oncology ,Virus Diseases ,Risk assessment ,business - Abstract
Patients with cancer are at increased risk for developing infectious complications during the course of their disease and treatment. The following sections of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prevention and Treatment of Cancer-Related Infections provide an overview of the risk factors for infectious complications, recommendations for infectious risk categorization, and strategies for prevention of infections in high-risk patient populations with cancer. Individualized risk evaluation for infections and incorporation of preventative measures are essential components of the overall spectrum of cancer care, and may contribute to optimizing treatment outcomes for patients.
- Published
- 2012
29. A Red Hot Mess
- Author
-
Robbe Peetz and Alison G. Freifeld
- Abstract
These case studies illustrate infections encountered in hospitals among patients with compromised immune systems. As a result of immunocompromise, the patients are vulnerable to common and uncommon infections. These cases are carefully chosen to reflect the most frequently encountered infections in the patient population, with an emphasis on illustrations and lucid presentations to explain state-of-the-art approaches in diagnosis and treatment. Common and uncommon presentations of infections are presented while the rare ones are not emphasized. The cases are written and edited by clinicians and experts in the field. Each of these cases highlights the immune dysfunction that uniquely predisposed the patient to the specific infection, and the cases deal with infections in the cancer patient, infections in the solid organ transplant recipient, infections in the stem cell recipient, infections in patients receiving immunosuppressive drugs, and infections in patients with immunocompromise that is caused by miscellaneous conditions.
- Published
- 2016
30. An Introduction
- Author
-
Alison G. Freifeld
- Abstract
This chapter focuses on solid tumors and how they can be treated. Solid tumors, lymphomas, and leukemias represent a widely diverse array of cancers. Until recently, the general approach to treating all of them was to administer cytotoxic anticancer drugs that damage proliferating cells by interfering with mitosis and other essential steps in cellular replication. Localized solid tumors are largely treated by surgical resection and radiotherapy, with cytotoxic chemotherapy being commonly used adjunctively or in cases of metastatic disease. A major drawback of this approach has been the lack of specificity in that cytotoxic drugs will destroy actively dividing normal cells as well as malignant cells. The “shotgun approach” of using intensive cytotoxic chemotherapies has been the mainstay of cancer treatment for at least 6 decades. The chapter concludes that in addition to the tissue damage and immunomodulating effects of anticancer drugs, it should be remembered that cancers themselves may increase the chances for infection.
- Published
- 2016
31. A New Rapid Method for Clostridium difficile DNA Extraction and Detection in Stool
- Author
-
Peter C. Iwen, Christine S. Booth, Hendrik J. Viljoen, Alison G. Freifeld, Xing Zhao, Teresa Karre, Scott E. Whitney, and Kari A. Simonsen
- Subjects
Clostridium difficile DNA ,Lysis ,Extraction (chemistry) ,Diagnostic test ,Biology ,Clostridium difficile ,DNA extraction ,Pathology and Forensic Medicine ,law.invention ,Microbiology ,law ,Molecular Medicine ,Polymerase chain reaction ,Point of care - Abstract
We describe a new method for the rapid diagnosis of Clostridium difficile infection, with stool sample preparation and DNA extraction by heat and physical disruption in a single-use lysis microreactor (LMR), followed by a rapid PCR amplification step. All steps can be accomplished in
- Published
- 2012
32. Invasive Non-Aspergillus Mold Infections in Transplant Recipients, United States, 2001–2006
- Author
-
Elias Anaissie, Dimitrios P. Kontoyiannis, Alison G. Freifeld, Loreen A. Herwaldt, Carol A. Kauffman, Thomas J. Walsh, Lisa Brumble, Mindy G. Schuster, Kieren A. Marr, Peter G. Pappas, Trish M. Perl, Benjamin J. Park, Kathleen Wannemuehler, Randall C. Walker, James I. Ito, Thomas F. Patterson, Genovefa A. Papanicolaou, Janice M. Brown, Barbara D. Alexander, David R. Andes, G. Marshall Lyon, Vicki A. Morrison, John W. Baddley, John R. Wingard, and Susan Hadley
- Subjects
Male ,Antifungal Agents ,Epidemiology ,fusariosis ,lcsh:Medicine ,organ transplant ,mucormycosis ,Cohort Studies ,invasive mold infections ,Fusarium ,CME ,Cumulative incidence ,non-Aspergillus ,biology ,Incidence ,Incidence (epidemiology) ,Mortality rate ,zygomycosis ,Middle Aged ,Infectious Diseases ,surgical procedures, operative ,surveillance ,Mucorales ,Female ,Adult ,Microbiology (medical) ,medicine.medical_specialty ,Opportunistic Infections ,Article ,lcsh:Infectious and parasitic diseases ,Internal medicine ,medicine ,Humans ,lcsh:RC109-216 ,Scedosporium ,Transplantation ,Aspergillus ,Research ,Mucormycosis ,lcsh:R ,biology.organism_classification ,medicine.disease ,United States ,Surgery ,Mycoses ,fungi ,Follow-Up Studies - Abstract
Recent reports describe increasing incidence of non-Aspergillus mold infections in hematopoietic cell transplant (HCT) and solid organ transplant (SOT) recipients. To investigate the epidemiology of infections with Mucorales, Fusarium spp., and Scedosporium spp. molds, we analyzed data from the Transplant-Associated Infection Surveillance Network, 23 transplant centers that conducted prospective surveillance for invasive fungal infections during 2001–2006. We identified 169 infections (105 Mucorales, 37 Fusarium spp., and 27 Scedosporium spp.) in 169 patients; 124 (73.4%) were in HCT recipients, and 45 (26.6%) were in SOT recipients. The crude 90-day mortality rate was 56.6%. The 12-month mucormycosis cumulative incidence was 0.29% for HCT and 0.07% for SOT. Mucormycosis incidence among HCT recipients varied widely, from 0.08% to 0.69%, with higher incidence in cohorts receiving transplants during 2003 and 2004. Non-Aspergillus mold infections continue to be associated with high mortality rates. The incidence of mucormycosis in HCT recipients increased substantially during the surveillance period.
- Published
- 2011
33. False-positiveAspergillusgalactomannan assay in solid organ transplant recipients with histoplasmosis
- Author
-
Carol A. Kauffman, Paschalis Vergidis, L. J. Wheat, Alison G. Freifeld, R. C. Walker, Daniel R. Kaul, D. C. Slagle, and A. K. Kressel
- Subjects
Adult ,Antigens, Fungal ,Histoplasma ,Enzyme-Linked Immunosorbent Assay ,Aspergillosis ,Histoplasmosis ,Microbiology ,Mannans ,Galactomannan ,chemistry.chemical_compound ,Antigen ,medicine ,Humans ,False Positive Reactions ,Transplantation ,Aspergillus ,biology ,Inhalation ,medicine.diagnostic_test ,business.industry ,Galactose ,Organ Transplantation ,Middle Aged ,biology.organism_classification ,medicine.disease ,Infectious Diseases ,Bronchoalveolar lavage ,chemistry ,Immunology ,Female ,business - Abstract
Post-transplantation histoplasmosis may be acquired via inhalation, may result from endogenous reactivation, or may be derived from the allograft. The Histoplasma and Aspergillus enzyme-linked immunoassays are increasingly being relied upon for rapid diagnosis of fungal infections, especially in immunocompromised patients. We describe 4 cases of solid organ transplant recipients who had histoplasmosis and a falsely positive Aspergillus galactomannan (GM) obtained from the serum or bronchoalveolar lavage (BAL) fluid. We also report our experience, testing for Histoplasma antigen (Ag) in specimens positive for Aspergillus GM. From January 2007 through December 2010, of 2432 unique patients who had positive Aspergillus GM tests, 514 (21%) were tested for Histoplasma Ag, and 27 were found to be positive. Most specimens that tested positive for both Aspergillus and Histoplasma were obtained by BAL. False-positive tests for Aspergillus GM can occur in immunosuppressed patients who have histoplasmosis, and may obscure the correct diagnosis.
- Published
- 2011
34. Executive Summary: Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: 2010 Update by the Infectious Diseases Society of America
- Author
-
Issam I Raad, Alison G. Freifeld, Kent A. Sepkowitz, John R. Wingard, Kenneth V. I. Rolston, James I. Ito, Michael Boeckh, Craig A. Mullen, Jo Anne H. Young, and Eric J. Bow
- Subjects
Microbiology (medical) ,medicine.medical_specialty ,Executive summary ,Leukopenia ,medicine.drug_class ,business.industry ,Antibiotics ,Cancer ,Guideline ,Neutropenia ,Antimicrobial ,medicine.disease ,Clinical trial ,Infectious Diseases ,medicine ,medicine.symptom ,Intensive care medicine ,business - Abstract
This document updates and expands the initial Infectious Diseases Society of America (IDSA) Fever and Neutropenia Guideline that was published in 1997 and first updated in 2002. It is intended as a guide for the use of antimicrobial agents in managing patients with cancer who experience chemotherapy-induced fever and neutropenia. Recent advances in antimicrobial drug development and technology, clinical trial results, and extensive clinical experience have informed the approaches and recommendations herein. Because the previous iteration of this guideline in 2002, we have a developed a clearer definition of which populations of patients with cancer may benefit most from antibiotic, antifungal, and antiviral prophylaxis. Furthermore, categorizing neutropenic patients as being at high risk or low risk for infection according to presenting signs and symptoms, underlying cancer, type of therapy, and medical comorbidities has become essential to the treatment algorithm. Risk stratification is a recommended starting point for managing patients with fever and neutropenia. In addition, earlier detection of invasive fungal infections has led to debate regarding optimal use of empirical or preemptive antifungal therapy, although algorithms are still evolving. What has not changed is the indication for immediate empirical antibiotic therapy. It remains true that all patients who present with fever and neutropenia should be treated swiftly and broadly with antibiotics to treat both gram-positive and gram-negative pathogens. Finally, we note that all Panel members are from institutions in the United States or Canada; thus, these guidelines were developed in the context of North American practices. Some recommendations may not be as applicable outside of North America, in areas where differences in available antibiotics, in the predominant pathogens, and/or in health care–associated economic conditions exist. Regardless of venue, clinical vigilance and immediate treatment are the universal keys to managing neutropenic patients with fever and/or infection.
- Published
- 2011
35. Reduction in False-Positive Aspergillus Serum Galactomannan Enzyme Immunoassay Results Associated with Use of Piperacillin-Tazobactam in the United States
- Author
-
Angela M. Caliendo, Raymund R. Razonable, Maha Assi, Hong Nguyen, Alison G. Freifeld, Steven J. Norris, John R. Wingard, John W. Baddley, Lynn L. Estes, Lindsey R. Baden, Thomas J. Walsh, Chadi A. Hage, R B Kohler, Martin B. Kleiman, Ryan K. Shields, L. Joseph Wheat, Paschalis Vergidis, and Pranatharthi H. Chandrasekar
- Subjects
Serum ,Microbiology (medical) ,Penicillanic Acid ,Mycology ,Aspergillosis ,Microbiology ,Immunoenzyme Techniques ,Mannans ,Galactomannan ,chemistry.chemical_compound ,Humans ,Medicine ,False Positive Reactions ,Aged, 80 and over ,Piperacillin ,chemistry.chemical_classification ,Aspergillus ,medicine.diagnostic_test ,biology ,Diagnostic Tests, Routine ,business.industry ,Galactose ,Serum specimen ,medicine.disease ,biology.organism_classification ,United States ,Anti-Bacterial Agents ,Piperacillin, Tazobactam Drug Combination ,Enzyme ,chemistry ,Immunoassay ,Piperacillin/tazobactam ,Female ,Drug Contamination ,business ,medicine.drug - Abstract
Piperacillin-tazobactam (PTZ) is known to cause false-positive results in the Platelia Aspergillus enzyme-linked immunoassay (EIA), due to contamination with galactomannan (GM). We tested 32 lots of PTZ and 27 serum specimens from patients receiving PTZ. GM was not detected in the lots of PTZ; one serum specimen (3.7%) was positive. PTZ formulations commonly used in the United States today appear to be a rare cause for false-positive GM results.
- Published
- 2014
36. Editorial Commentary: Viridans Group Streptococci in Febrile Neutropenic Cancer Patients: What Should We Fear?
- Author
-
Raymund R. Razonable and Alison G. Freifeld
- Subjects
Microbiology (medical) ,medicine.medical_specialty ,biology ,business.industry ,Cancer ,medicine.disease ,biology.organism_classification ,Infectious Diseases ,Viridans streptococci ,Internal medicine ,Bloodstream infection ,medicine ,Intensive care medicine ,business ,Febrile neutropenia - Published
- 2014
37. The Role of Second-Generation Antifungal Triazoles for Treatment of the Endemic Mycoses
- Author
-
J. Ryan Bariola, David R. Andes, and Alison G. Freifeld
- Subjects
Voriconazole ,Posaconazole ,medicine.medical_specialty ,Drug intolerance ,Biology ,medicine.disease ,Asymptomatic ,Histoplasmosis ,Infectious Diseases ,Amphotericin B ,Immunology ,medicine ,medicine.symptom ,Intensive care medicine ,Adverse effect ,Blastomycosis ,medicine.drug - Abstract
Endemic fungi are geographically restricted to certain areas of the United States where they are typically found in soil. They often cause asymptomatic or self-limited flu-like infections in humans. Occasionally, they cause serious human disease including acute or chronic pneumonias, or bone, skin, or central nervous system disease. Amphotericin B and first-generation triazoles are standard therapy for serious endemic fungal infections. Adverse effects, drug intolerance, and rare refractory infections may limit their use; therefore, experience is increasing using newer triazoles (voriconazole and posaconazole) to potentially circumvent these problems. This article reviews the basic scientific information and clinical experience using triazoles for treating endemic fungal infections.
- Published
- 2010
38. Seronegative naturally acquired West Nile virus encephalitis in a renal and pancreas transplant recipient
- Author
-
R.D. McComb, S.A. Kazmi, Alison G. Freifeld, Scott A. Koepsell, and Anthony R. Sambol
- Subjects
Transplantation ,biology ,business.industry ,animal diseases ,viruses ,medicine.medical_treatment ,virus diseases ,Immunosuppression ,Nucleic acid amplification technique ,medicine.disease ,biology.organism_classification ,Virology ,Virus ,nervous system diseases ,Serology ,Flavivirus ,Infectious Diseases ,Immunoglobulin M ,Immunology ,biology.protein ,medicine ,business ,Encephalitis - Abstract
West Nile virus (WNV), a single-stranded RNA flavivirus, has spread across the United States since arriving in 1999. While asymptomatic or self-limited in a majority of patients, WNV can cause a severe neuroinvasive disease, which occurs more often in transplant recipients with chronic immunosuppression. Diagnosis of acute WNV infection usually relies on serologic identification of immunoglobulin M (IgM) specific for the virus. We report a fatal case of naturally acquired WNV encephalitis in a renal and pancreas transplant recipient who was seronegative for WNV-specific IgM but had detectable WNV RNA by nucleic acid amplification testing (NAAT) several weeks after the onset of symptoms. This case demonstrates the importance of using both serologic assays and NAAT for WNV in transplant recipients with the clinical suspicion of encephalitis.
- Published
- 2010
39. Prospective Surveillance for Invasive Fungal Infections in Hematopoietic Stem Cell Transplant Recipients, 2001–2006: Overview of the Transplant‐Associated Infection Surveillance Network (TRANSNET) Database
- Author
-
Dimitrios P. Kontoyiennis, Vicki A. Morrison, Trish M. Perl, James I. Ito, John W. Baddley, Thomas F. Patterson, Alison G. Freifeld, David R. Andes, Randall C. Walker, Tom M. Chiller, Lisa Brumble, Carol A. Kauffman, Barbara D. Alexander, Katherine M. Knapp, Kieren A. Marr, Genovefa A. Papanicolaou, Janice M. Brown, Elias Anaissie, Peter G. Pappas, Benjamin J. Park, Mindy G. Schuster, Kathleen A. Wannemuehler, John R. Wingard, Susan Hadley, Thomas J. Walsh, G. Marshall Lyon, and Loreen A. Herwaldt
- Subjects
Adult ,Male ,Microbiology (medical) ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Aspergillosis ,Cohort Studies ,Immunocompromised Host ,Young Adult ,Internal medicine ,medicine ,Humans ,Cumulative incidence ,Prospective Studies ,Child ,Prospective cohort study ,Aged ,Infection Control ,business.industry ,Incidence ,Incidence (epidemiology) ,Hematopoietic Stem Cell Transplantation ,Infant ,Retrospective cohort study ,Middle Aged ,medicine.disease ,United States ,Surgery ,Transplantation ,surgical procedures, operative ,Infectious Diseases ,Mycoses ,Child, Preschool ,Female ,Zygomycosis ,business ,Sentinel Surveillance - Abstract
Background The incidence and epidemiology of invasive fungal infections (IFIs), a leading cause of death among hematopoeitic stem cell transplant (HSCT) recipients, are derived mainly from single-institution retrospective studies. Methods The Transplant Associated Infections Surveillance Network, a network of 23 US transplant centers, prospectively enrolled HSCT recipients with proven and probable IFIs occurring between March 2001 and March 2006. We collected denominator data on all HSCTs preformed at each site and clinical, diagnostic, and outcome information for each IFI case. To estimate trends in IFI, we calculated the 12-month cumulative incidence among 9 sequential subcohorts. Results We identified 983 IFIs among 875 HSCT recipients. The median age of the patients was 49 years; 60% were male. Invasive aspergillosis (43%), invasive candidiasis (28%), and zygomycosis (8%) were the most common IFIs. Fifty-nine percent and 61% of IFIs were recognized within 60 days of neutropenia and graft-versus-host disease, respectively. Median onset of candidiasis and aspergillosis after HSCT was 61 days and 99 days, respectively. Within a cohort of 16,200 HSCT recipients who received their first transplants between March 2001 and September 2005 and were followed up through March 2006, we identified 718 IFIs in 639 persons. Twelve-month cumulative incidences, based on the first IFI, were 7.7 cases per 100 transplants for matched unrelated allogeneic, 8.1 cases per 100 transplants for mismatched-related allogeneic, 5.8 cases per 100 transplants for matched-related allogeneic, and 1.2 cases per 100 transplants for autologous HSCT. Conclusions In this national prospective surveillance study of IFIs in HSCT recipients, the cumulative incidence was highest for aspergillosis, followed by candidiasis. Understanding the epidemiologic trends and burden of IFIs may lead to improved management strategies and study design.
- Published
- 2010
40. A model of tuberculosis transmission and intervention strategies in an urban residential area
- Author
-
Hendrik J. Viljoen, Elsje Pienaar, Alison G. Freifeld, Aaron M. Fluitt, and Scott E. Whitney
- Subjects
Tuberculosis ,Urban Population ,Population ,Disease ,Models, Biological ,Biochemistry ,Article ,Structural Biology ,Intervention (counseling) ,medicine ,Humans ,education ,Simulation ,geography ,education.field_of_study ,geography.geographical_feature_category ,Transmission (medicine) ,business.industry ,Organic Chemistry ,Urban Health ,medicine.disease ,Residential area ,Vaccination ,Computational Mathematics ,Public transport ,business ,Demography - Abstract
The model herein aims to explore the dynamics of the spread of tuberculosis (TB) in an informal settlement or township. The population is divided into households of various sizes and also based on commuting status. The model dynamics distinguishes between three distinct social patterns: the exposure of commuters during travel, random diurnal interaction and familial exposure at night. Following the general SLIR models, the population is further segmented into susceptible (S), exposed/latently infected (L), active/infectious (I), and recovered (R) individuals. During the daytime, commuters travel on public transport, while non-commuters randomly interact in the community to mimic chance encounters with infectious persons. At night, each family interacts and sleeps together in the home. The risk of exposure to TB is based on the proximity, duration, and frequency of encounters with infectious persons. The model is applied to a hypothetical population to explore the effects of different intervention strategies including vaccination, wearing of masks or scarves during the commute, prophylactic treatment of latent infections and more effective case-finding and treatment. The most important findings of the model are: (1) members of larger families are responsible for more disease transmissions than those from smaller families, (2) daily commutes on public transport provide ideal conditions for transmission of the disease, (3) improved diagnosis and treatment has the greatest impact on the spread of the disease, and (4) detecting TB at the first clinic visit, when patients are still smear negative, is key.
- Published
- 2010
41. Seroprevalence of West Nile virus infection in solid organ transplant recipients
- Author
-
Alison G. Freifeld, Anthony R. Sambol, Beth K. Schweitzer, Andre C. Kalil, Laura R. Shafer, and Jane L. Meza
- Subjects
Adult ,Male ,medicine.medical_specialty ,viruses ,Population ,Enzyme-Linked Immunosorbent Assay ,Antibodies, Viral ,Organ transplantation ,Disease Outbreaks ,Midwestern United States ,Serology ,Cohort Studies ,Seroepidemiologic Studies ,medicine ,Humans ,Seroprevalence ,education ,Aged ,Transplantation ,education.field_of_study ,biology ,business.industry ,virus diseases ,Outbreak ,Organ Transplantation ,Hemagglutination Inhibition Tests ,Middle Aged ,medicine.disease ,biology.organism_classification ,Virology ,nervous system diseases ,Flavivirus ,Infectious Diseases ,Immunoglobulin G ,Immunology ,Saint Louis encephalitis ,Female ,business ,West Nile virus ,West Nile Fever - Abstract
A.G. Freifeld, J. Meza, B. Schweitzer, L. Shafer, A.C. Kalil. A.R. Sambol. Seroprevalence of West Nile virus infection in solid organ transplant recipients. Transpl Infect Dis 2010: 12: 120–126. All rights reserved Background. Of people infected with mosquito-borne West Nile virus (WNV)
- Published
- 2010
42. Histoplasmosis in solid organ transplant recipients: early diagnosis and treatment
- Author
-
L. Joseph Wheat, Alison G. Freifeld, and Daniel R. Kaul
- Subjects
medicine.medical_specialty ,Pediatrics ,Antifungal Agents ,Antigens, Fungal ,Fever ,Urinalysis ,Biopsy ,Treatment outcome ,Mycology ,Histoplasmosis ,Predictive Value of Tests ,X ray computed ,Epidemiology ,Humans ,Immunology and Allergy ,Medicine ,Intensive care medicine ,Transplantation ,medicine.diagnostic_test ,business.industry ,Organ Transplantation ,medicine.disease ,Early Diagnosis ,Treatment Outcome ,Predictive value of tests ,Tomography, X-Ray Computed ,business ,Solid organ transplantation - Abstract
To present current knowledge about the epidemiology, clinical presentation, diagnosis and treatment of histoplasmosis in solid organ transplant (SOT) recipients.Histoplasmosis is rare in SOT patients, and most cases have been reported from large transplant centers in the Midwestern USA, where the fungus is endemic. Urine antigen testing and the chest computed tomography scan are emerging as especially useful diagnostic tools in the SOT population. Standard treatments include liposomal amphotericin b followed by itraconazole, but newer azoles (voriconazole and posaconazole) have good in-vitro activity and have been successfully used in some SOT cases.Clinical suspicion is essential to early recognition of histoplasmosis in SOT patients who often present with fever of unknown cause and pulmonary symptoms. Diagnosis is usually made by a combinatorial approach, including antigen tests, radiology and appropriate biopsies for culture and histology. Treatment with available antifungals is associated with more than 95% success.
- Published
- 2009
43. Cerebral aspergillosis caused byAspergillus ustusfollowing orthotopic heart transplantation: case report and review of the literature
- Author
-
Mohammed A. Quader, Peter C. Iwen, Diana F. Florescu, Andre C. Kalil, Ioana Dumitru, Alison G. Freifeld, and Lisa A. Hill
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,medicine.medical_treatment ,Aspergillosis ,Immunocompromised Host ,Fatal Outcome ,Postoperative Complications ,Aspergillus ustus ,Cerebral aspergillosis ,medicine ,Humans ,Mycosis ,Aspergillus species ,Heart transplantation ,Brain Diseases ,Transplantation ,business.industry ,medicine.disease ,Molecular analysis ,Aspergillus ,Heart Transplantation ,business - Abstract
This report describes the first case of cerebral aspergillosis in a heart transplantation patient caused by Aspergillus ustus and reviews 15 previously reported cases of invasive aspergillosis in immunocompromised hosts caused by this mold. The utility of molecular analysis for the identification of unusual fungal pathogens is also described. The refractory nature of A. ustus to treatment is similar to other Aspergillus species and treatment options are reviewed.
- Published
- 2009
44. Pharmacoeconomic Analysis of Microbiologic Techniques for Differentiating Staphylococci Directly from Blood Culture Bottles
- Author
-
Jodi L. Garrett, Elizabeth D. Hermsen, Amy A. Armbrust, Peter C. Iwen, Donald G. Klepser, Mark E. Rupp, Alison G. Freifeld, and Sara S. Shull
- Subjects
Coagulase ,Microbiology (medical) ,Staphylococcus aureus ,Micrococcaceae ,Cost-Benefit Analysis ,Patient risk ,medicine.disease_cause ,Polymerase Chain Reaction ,Sensitivity and Specificity ,law.invention ,Microbiology ,Risk Factors ,law ,medicine ,Humans ,Blood culture ,In Situ Hybridization ,biology ,medicine.diagnostic_test ,Bacteriology ,Staphylococcal Infections ,biology.organism_classification ,Coagulase test ,Gram staining ,Blood culture bottles ,Costs and Cost Analysis ,Staphylococcus - Abstract
Differentiating staphylococci in blood cultures is a critical issue, particularly when only one of two cultures is positive by Gram staining for staphylococci. New tests for the identification of Staphylococcus aureus allow faster results and definitive treatment compared to the tube coagulase test interpreted at 24 h (TCT24). These newer tests, peptide nucleic acid fluorescence in situ hybridization (PNA-FISH) and real-time PCR (RT-PCR), offer improved sensitivity at higher cost. Data suggest that the tube coagulase test may be interpreted at 4 h (TCT4) with little loss of sensitivity. The impact of variability in turnaround time, sensitivity, specificity, and cost on comparative cost-effectiveness is unknown. Our aim was to establish the cost-effectiveness of TCT24, PNA-FISH, RT-PCR, and TCT4 for direct identification of staphylococci in blood cultures. Decision analysis comparing these strategies was done from the institutional perspective. Besides test variables, other variables included patient risk factors, empirical treatment, and follow-up cultures. Probability and cost estimates came from the literature and institutional data. Base case estimates were derived from institutional rates of 73% contamination when coagulase-negative staphylococci were identified, 67.6% prevalence of risk factors, and 12.4% prevalence of S. aureus when one of two cultures yielded staphylococci. Sensitivity analysis was done across a range of probabilities and costs. In the base case, TCT4 and TCT24 were more cost-effective than RT-PCR and PNA-FISH ($78 versus $120 versus $165 per patient, respectively). The advantage of TCT4 and TCT24 remained robust upon sensitivity analysis. TCT4 should be further evaluated as a rapid, cost-effective means for identification of S. aureus in blood cultures.
- Published
- 2008
45. Higher Risk of Cytomegalovirus and Aspergillus Infections in Recipients of T Cell–Depleted Unrelated Bone Marrow: Analysis of Infectious Complications in Patients Treated with T Cell Depletion Versus Immunosuppressive Therapy to Prevent Graft-versus-Host Disease
- Author
-
Kevin P. High, Nancy A. Kernan, John E. Wagner, Shelly L. Carter, Genovefa A. Papanicolaou, Alison G. Freifeld, Jo Anne H. Van Burik, Kamar Godder, Adam Mendizabal, and Saul Yanovich
- Subjects
Male ,Opportunistic infection ,medicine.medical_treatment ,Cytomegalovirus ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Aspergillosis ,Gastroenterology ,Cohort Studies ,0302 clinical medicine ,Medicine ,Bone Marrow Transplantation ,Incidence ,Hematopoietic Stem Cell Transplantation ,Hematology ,3. Good health ,surgical procedures, operative ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Cytomegalovirus Infections ,Cyclosporine ,Female ,T cell depletion ,Immunosuppressive Agents ,medicine.drug ,Adult ,medicine.medical_specialty ,Adolescent ,Congenital cytomegalovirus infection ,Opportunistic Infections ,Lymphocyte Depletion ,03 medical and health sciences ,Internal medicine ,Humans ,Transplantation, Homologous ,Retrospective Studies ,Immunosuppression Therapy ,Transplantation ,business.industry ,medicine.disease ,Survival Analysis ,Methotrexate ,Graft-versus-host disease ,Immunology ,Bone marrow ,business ,030215 immunology - Abstract
Serious infections are a major obstacle limiting the usefulness of unrelated donor marrow transplantation. Graft-versus-host disease (GVHD) and its therapy are associated with a high risk of opportunistic infection. In this study, patients were randomized to receive 1 of 2 GVHD prophylaxis strategies, marrow T cell depletion, and cyclosporine (TCD) or methotrexate/cyclosporine (M/C) after transplantation. The patients underwent transplantation between March 1995 and October 2000 as part of a multicenter randomized trial. As a secondary analysis, we analyzed infections in this study cohort. Among the 404 patients who underwent transplantation, a total of 1598 infections were reported. The rates of serious and fatal infections did not differ between the TCD and M/C groups. Bacterial infections accounted for 1/3 of serious infections in each treatment arm. A significantly higher incidence of severe cytomegalovirus (CMV) and life-threatening or fatal aspergillus infections was observed in the patients receiving TCD (CMV, 28% vs 17% [P = .02]; aspergillosis, 16% vs 7% [P < .01]). The only independent risk factor for serious infection was the development of grade III-IV acute GVHD (aGVHD; hazard ratio = 1.41; 95% confidence interval = 1.03-1.91). Strategies to speed immune recovery, even in the absence of GVHD, are needed to overcome the risk of infection after unrelated donor transplantation.
- Published
- 2007
46. Cytomegalovirus viremia in solid organ transplantation: does the initial viral load correlate with risk factors and outcomes?
- Author
-
Lucy Wrenshall, Susan E. Puumala, Penny Hardiman, Catherine L. Gebhart, Alison G. Freifeld, Alan Norman Langnas, Andre C. Kalil, Kim Bargenquast, and Josh Levitsky
- Subjects
Human cytomegalovirus ,Transplantation ,biology ,Opportunistic infection ,business.industry ,virus diseases ,Viremia ,biology.organism_classification ,medicine.disease ,Betaherpesvirinae ,Immunology ,medicine ,Viral disease ,Risk factor ,business ,Viral load - Abstract
Consistent data for using CMV quantitative PCR (QnPCR) on initial presentation to predict outcomes after solid organ transplantation (SOT) are lacking. Recipients with measurable CMV QnPCR and either CMV-V (asymptomatic viremia) or CMV-D (symptomatic CMV infection) were analyzed over 24 months. Risk factors and outcomes were evaluated in relation to initial QnPCR by regression analysis and time-to-event curves. Twenty-eight recipients were identified: five CMV-V, 23 CMV-D. Patients with CMV-D had a higher median initial QnPCR (230 000 copies/mL) compared with CMV-V (2500 copies/mL; p 10 000 copies/mL compared with 83% of the CMV-D (p = 0.004). The initial QnPCR was higher (250 000 copies/mL) in patients who did not clear CMV PCR than those who cleared (8000 copies/mL) after 14 d of treatment (p = 0.03). Risk factors and indirect CMV effects were not associated with initial QnPCR. Our results highlight the importance of the initial CMV QnPCR in relation to the development of symptomatic CMV and a slower response to therapy. Alternatively, late asymptomatic viremia and recurrent CMV are associated with lower PCR levels and a low likelihood to progress and result in clinical disease.
- Published
- 2007
47. Mucor circinelloides Was Identified by Molecular Methods as a Cause of Primary Cutaneous Zygomycosis
- Author
-
Rhonda K. Noel, Alison G. Freifeld, Lynne Sigler, and Peter C. Iwen
- Subjects
Male ,Microbiology (medical) ,Hypha ,Sequence analysis ,Molecular Sequence Data ,Case Reports ,Polymerase Chain Reaction ,Microbiology ,medicine ,Dermatomycoses ,Humans ,Mucormycosis ,Internal transcribed spacer ,DNA, Fungal ,Mycological Typing Techniques ,Aged, 80 and over ,Mucor ,biology ,Genetic heterogeneity ,Sequence Analysis, DNA ,medicine.disease ,biology.organism_classification ,Phenotype ,Mucor circinelloides ,Zygomycosis - Abstract
A case of primary cutaneous zygomycosis caused by Mucor circinelloides is described. Histopathology showed typical hyphae along with chlamydospores. The isolate was identified by molecular and phenotypic methods. The utility of sequence analysis of the internal transcribed spacer region is highlighted; however, further studies are needed to assess species genetic heterogeneity.
- Published
- 2007
48. Respiratory Syncytial Virus in Hematopoietic Stem Cell Transplantation and Solid-Organ Transplantation
- Author
-
Kari Neemann and Alison G. Freifeld
- Subjects
education.field_of_study ,Viral culture ,business.industry ,Ribavirin ,medicine.medical_treatment ,Population ,Hematopoietic stem cell transplantation ,Disease ,Virus ,chemistry.chemical_compound ,Infectious Diseases ,medicine.anatomical_structure ,chemistry ,Immunology ,medicine ,Risk factor ,education ,business ,Respiratory tract - Abstract
Respiratory syncytial virus (RSV), one of the most common causes of respiratory infections in immunocompetent individuals, can cause significant pulmonary morbidity and mortality in hematopoietic stem cell (HSCT) and less often in solid-organ transplant recipients. Early diagnosis and medical intervention prior to the progression from upper to lower respiratory tract viral involvement is essential to positively affect the clinical course. The greatest risk of disease progression from upper to lower respiratory tract disease is during the early posttransplant period for HSCT recipients, with lymphopenia being an important risk factor. Polymerase chain reaction has become the preferred method for rapidly diagnosing infection in this population because of higher sensitivity compared to traditional viral culture and direct viral antigen methods. Despite the lack of prospective randomized trials, retrospective pooled analyses have suggested that systemically delivered ribavirin (either aerosolized, oral, or IV; with or without immunomodulator therapy) can decrease the risk of progression of disease. Additionally, there are a number of clinical trials currently in process to evaluate several new agents that target RSV in the high-risk HSCT patient population.
- Published
- 2015
49. BK DNA Viremia as Predictor of Hemorrhagic Cystitis (HC) in Adults During the First 100 Days After Allogeneic Hematopoietic Stem Cell Transplantation (AlloHSCT)
- Author
-
Alison G. Freifeld, Mohammad Awaji, Jane L. Meza, Catherine L. Gebhart, Luis Guzman, R. Gregory Bociek, and Valerie Shostrom
- Subjects
business.industry ,medicine.medical_treatment ,Viremia ,Hematopoietic stem cell transplantation ,medicine.disease ,Virology ,chemistry.chemical_compound ,Infectious Diseases ,Oncology ,chemistry ,Immunology ,medicine ,business ,DNA ,Hemorrhagic cystitis - Published
- 2015
50. Survey of Clostridium difficile Prescribing Practices for Hematology/Oncology Patients
- Author
-
Alison G. Freifeld, Laura Gleason, Donald G. Klepser, Kiri Rolek, and Susanne Liewer
- Subjects
Pediatrics ,medicine.medical_specialty ,Infectious Diseases ,Oncology ,business.industry ,medicine ,Clostridium difficile ,Intensive care medicine ,business ,Hematology+Oncology - Published
- 2015
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.