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Population-Level Burden of Delayed or In Vitro Discordant Empiric Antibiotics Among Bacteremic Patients at US Hospitals
- Sameer Kadri, Yi Ling Lai, Sarah Warner, Jeffrey R. Strich, Ahmed Babiker, Emily Ricotta, John P. Dekker, Tara Palmore, Chanu Rhee, Michael Klompas, David Hooper, John H. Powers, Robert L. Danner, Jennifer Adjemian
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- Journal:
- Infection Control & Hospital Epidemiology / Volume 41 / Issue S1 / October 2020
- Published online by Cambridge University Press:
- 02 November 2020, pp. s44-s45
- Print publication:
- October 2020
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Background: Delayed or in vitro inactive empiric antibiotic therapy may be detrimental to survival in patients with bloodstream infections (BSIs). Understanding the landscape of delayed or discordant empiric antibiotic therapy (DDEAT) across different patient, pathogen, and hospital types, as well as by their baseline resistance milieu, may enable providers, antimicrobial stewardship programs, and policy makers to optimize empiric prescribing. Methods: Inpatients with clinically suspected serious infection (based on sampling of blood cultures and receiving systemic antibiotic therapy on the same or next day) found to have BSI were identified in the Cerner Healthfacts EHR database. Patients were considered to have received DDEAT when, on culture sampling day, they received either no antibiotic(s) or none that displayed in vitro activity against the pathogenic bloodstream isolate. Antibiotic-resistant phenotypes were defined by in vitro resistance to taxon-specific prototype antibiotics (eg, methicillin/oxacillin resistance in S. aureus) and were used to estimate baseline resistance prevalence encountered by the hospital. The probability of DDEAT was examined by bacterial taxon, by time of BSI onset, and by presence versus absence of antibiotic-resistance phenotypes, sepsis or septic shock, hospital type, and baseline resistance. Results: Of 26,036 assessable patients with a BSI at 131 US hospitals between 2005 and 2014, 14,658 (56%) had sepsis, 3,623 (14%) had septic shock, 5,084 (20%) had antibiotic-resistant phenotypes, and 8,593 (33%) received DDEAT. Also, 4,428 (52%) recipients of DDEAT received no antibiotics on culture sampling day, whereas the remaining 4,165 (48%) received in vitro discordant therapy. DDEAT occurred most often in S. maltophilia (87%) and E. faecium (80%) BSIs; however, 75% of DDEAT cases and 76% of deaths among recipients of DDEAT collectively occurred among patients with S. aureus and Enterobacteriales BSIs. For every 8 bacteremic patients presenting with septic shock, 1 patient did not receive any antibiotics on culture day (Fig. 1A). Patients with BSIs of hospital (vs community) onset were twice as likely to receive no antibiotics on culture day, whereas those with bloodstream pathogens displaying antibiotic-resistant (vs susceptible) phenotypes were 3 times as likely to receive in vitro discordant therapy (Fig. 1B). The median proportion of DDEAT ranged between 25% (14, 37%) in eight <300-bed teaching hospitals in the lowest baseline resistance quartile and 40% (31, 50%) at five ≥300-bed teaching hospitals in the third baseline resistance quartile (Fig. 2). Conclusions: Delayed or in vitro discordant empiric antibiotic therapy is common among patients with BSI in US hospitals regardless of hospital size, teaching status, or local resistance patterns. Prompt empiric antibiotic therapy in septic shock and hospital-onset BSI needs more support. Reliable detection of S. aureus and Enterobacteriales bloodstream pathogens and their resistance patterns earlier with rapid point-of-care diagnostics may mitigate the population-level impact of DDEAT in BSI.
Funding: This study was funded in part by the National Institutes of Health Clinical Center, National Institutes of Allergy and Infectious Diseases, National Cancer Institute (NCI contract no. HHSN261200800001E) and the Agency for Healthcare Research and Quality.
Disclosures: None
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- By Agoston T. Agoston, Syed Z. Ali, Mahul B. Amin, Daniel A. Arber, Pedram Argani, Sylvia L. Asa, Rebecca N. Baergen, Zubair W. Baloch, Andrew M. Bellizzi, Kurt Benirschke, Allen Burke, Kenneth B. Calder, Karen L. Chang, Rebecca D. Chernock, Wang Cheung, Thomas V. Colby, Byron P. Croker, Ronald A. DeLellis, Edward F. DiCarlo, Ralph C. Eagle, Hormoz Ehya, Brett M. Elicker, Tarik M. Elsheikh, Robert E. Fechner, Linda D. Ferrell, Melina B. Flanagan, Douglas B. Flieder, Christopher S. Foster, Lillian Gaber, Karuna Garg, Kim R. Geisinger, Ryan M. Gill, Eric F. Glassy, David J. Glembocki, Zachary D. Goodman, Robert O. Greer, David J. Grignon, Gerardo E. Guiter, Kymberly A. Gyure, Ian S. Hagemann, Michael R. Henry, Jason L. Hornick, Ralph H. Hruban, Phyllis C. Huettner, Peter A. Humphrey, Olga B. Ioffe, Edward C. Klatt, Michael J. Klein, Ernest E. Lack, James N. Lampros, Lester J. Layfield, Robin D. LeGallo, Kevin O. Leslie, James S. Lewis, Virginia A. LiVolsi, Alberto M. Marchevsky, Anne Marie McNicol, Mitra Mehrad, Elizabeth Montgomery, Cesar A. Moran, Christopher A. Moskaluk, George J. Netto, G. Petur Nielsen, Robert D. Odze, Arthur S. Patchefsky, James W. Patterson, Elizabeth N. Pavlisko, John D. Pfeifer, Celeste N. Powers, Richard A. Prayson, Anja C. Roden, Victor L. Roggli, Andrew E. Rosenberg, Sherif Said, Margie A. Scott, Raja R. Seethala, Carlie S. Sigel, Jan F. Silverman, Bruce R. Smoller, Edward B. Stelow, Nora C. J. Sun, Mark W. Teague, Satish K. Tickoo, Thomas M. Ulbright, Paul E. Wakely, Jun Wang, Lawrence M. Weiss, Mark R. Wick, Howard H. Wu, Rhonda K. Yantiss, Charles Zaloudek, Yaxia Zhang, Xiaohui Sheila Zhao
- Edited by Mark R. Wick, University of Virginia, Virginia A. LiVolsi, University of Pennsylvania School of Medicine, John D. Pfeifer, Washington University School of Medicine, St Louis, Edward B. Stelow, University of Virginia, Paul E. Wakely, Jr
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- Book:
- Silverberg's Principles and Practice of Surgical Pathology and Cytopathology
- Published online:
- 13 March 2015
- Print publication:
- 26 March 2015, pp vii-x
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Approval and Withdrawal of New Antibiotics and other Antiinfectives in the U.S., 1980–2009
- Kevin Outterson, John H. Powers, Enrique Seoane-Vazquez, Rosa Rodriguez-Monguio, Aaron S. Kesselheim
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- Journal:
- Journal of Law, Medicine & Ethics / Volume 41 / Issue 3 / Fall 2013
- Published online by Cambridge University Press:
- 01 January 2021, pp. 688-696
- Print publication:
- Fall 2013
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Antibiotic use triggers evolutionary and ecological responses from bacteria, leading to antibiotic resistance and harmful patient outcomes. Two complementary strategies support long-term antibiotic effectiveness: conservation of existing therapies and production of novel antibiotics. Conservation encompasses infection control, antibiotic stewardship, and other public health interventions to prevent infection, which reduce antibiotic demand. Production of new antibiotics allows physicians to replace existing drugs rendered less effective by resistance.
In recent years, physicians and policymakers have raised concerns about the pipeline for new antibiotics, pointing to a decline in the number of antibiotics approved since the 1980s. This trend has been attributed to high research and development costs, low reimbursement for antibiotics, and regulatory standards for review and approval. Professional societies and researchers around the world have called for renewed emphasis on antimicrobial stewardship, while also supporting antibiotic research and development through grants, changes to intellectual property laws to extend market exclusivity periods, and modification of premarket testing regulations to reduce antibiotic development time and expenses.
Contributors
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- By C. Alan Anderson, Celso Arango, David B. Arciniegas, Igor Bombin, Robert W. Buchanan, C. Robert Cloninger, Joshua Cosman, C. Munro Cullum, Felipe DeBrigard, Steven L. Dubovsky, Robert Feinstein, Lynne Fenton, Christopher M. Filley, Laura A. Flashman, Morris Freedman, Oliver Freudenreich, Kimberly L. Frey, Lauren C. Frey, Kelly S. Giovanello, Deborah A. Hall, John Hart, Kenneth M. Heilman, Katherine L. Howard, Robin A. Hurley, Daniel I. Kaufer, Sita Kedia, James P. Kelly, B. K. Kleinschmidt-DeMasters, Benzi M. Kluger, David G. Lichter, Deborah M. Little, Deborah M. Lucas, Thomas W. McAllister, Mario F. Mendez, Doron Merims, Steven G. Ojemann, Fred Ovsiew, Brian D. Power, Bruce H. Price, Gila Z. Reckess, Martin L. Reite, Matthew Rizzo, Donald C. Rojas, Michael Henry Rosenbloom, Elliott D. Ross, Jeremy D. Schmahmann, Stuart A. Schneck, Jonathan M. Silver, Mark C. Spitz, Sergio E. Starkstein, Katherine H. Taber, Robert L. Trestman, Hal S. Wortzel
- Edited by David B. Arciniegas, C. Alan Anderson, Christopher M. Filley
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- Book:
- Behavioral Neurology & Neuropsychiatry
- Published online:
- 05 February 2013
- Print publication:
- 24 January 2013, pp vii-x
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- By Nalini Vadivelu, Christian J. Whitney, Raymond S. Sinatra, M. Khurram Ghori, Yu-Fan (Robert) Zhang, Raymond S. Sinatra, Joshua Wellington, Yuan-Yi Chia, Francis J. Keefe, Jon McCormack, Ian Power, John Butterworth, P. M. Lavand’homme, M. F. De Kock, Bradley Urie, Oscar A. de Leon-Casasola, Frederick M. Perkins, Larry F. Chu, David Clark, Martin S. Angst, Cynthia M. Welchek, Lisa Mastrangelo, Raymond S. Sinatra, Richard Martinez, Scott S. Reuben, Asokumar Buvanendran, Raymond S. Sinatra, Pamela E Macintyre, Julia Coldrey, Daniel B. Maalouf, Spencer S. Liu, Susan Dabu-Bondoc, Samantha A. Franco, Raymond S. Sinatra, James Benonis, Jennifer Fortney, David Hardman, Gavin Martin, Holly Evans, Karen C. Nielsen, Marcy S. Tucker, Stephen M. Klein, Benjamin Sherman, Ikay Enu, Raymond S. Sinatra, James W. Heitz, Eugene R. Viscusi, Jonathan S. Jahr, Kofi N. Donkor, Raymond S. Sinatra, Manzo Suzuki, Johan Raeder, Vegard Dahl, Stefan Erceg, Keun Sam Chung, Kok-Yuen Ho, Tong J. Gan, Dermot R. Fitzgibbon, Paul Willoughby, Brian E. Harrington, Joseph Marino, Tariq M. Malik, Raymond S. Sinatra, Giorgio Ivani, Valeria Mossetti, Simona Italiano, Thomas M. Halaszynski, Nousheh Saidi, Javier Lopez, Kate Miller, Ferne Braveman, Jaya L. Varadarajan, Steven J. Weisman, Sukanya Mitra, Raymond S. Sinatra, Theodore J. Saclarides, Knox H. Todd, James R. Miner, Chris Pasero, Nancy Eksterowicz, Margo McCaffery, Leslie N. Schechter, Amr E. Abouleish, Govindaraj Ranganathan, Tee Yong Tan, Stephan A. Schug, Marie N. Hanna, Spencer S. Liu, Christopher L. Wu, Craig T. Hartrick, Garen Manvelian, Christine Miaskowski, Brian Durkin, Peter S. A. Glass
- Edited by Raymond S. Sinatra, Oscar A. de Leon-Cassasola, University of Rochester Medical Center, New York, Eugene R. Viscusi, Brian Ginsberg
- Foreword by Henry McQuay
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- Book:
- Acute Pain Management
- Published online:
- 26 October 2009
- Print publication:
- 27 April 2009, pp vii-xii
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Neurocognitive predictors of financial capacity across the dementia spectrum: Normal aging, mild cognitive impairment, and Alzheimer’s disease
- MEGAN G. SHEROD, H. RANDALL GRIFFITH, JACQUELYNN COPELAND, KATHERINE BELUE, SARA KRZYWANSKI, EDWARD Y. ZAMRINI, LINDY E. HARRELL, DAVID G. CLARK, JOHN C. BROCKINGTON, RICHARD E. POWERS, DANIEL C. MARSON
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- Journal:
- Journal of the International Neuropsychological Society / Volume 15 / Issue 2 / March 2009
- Published online by Cambridge University Press:
- 01 March 2009, pp. 258-267
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Financial capacity is a complex instrumental activity of daily living critical to independent functioning of older adults and sensitive to impairment in patients with amnestic mild cognitive impairment (MCI) and Alzheimer’s disease (AD). However, little is known about the neurocognitive basis of financial impairment in dementia. We developed cognitive models of financial capacity in cognitively healthy older adults (n = 85) and patients with MCI (n = 113) and mild AD (n = 43). All participants were administered the Financial Capacity Instrument (FCI) and a neuropsychological test battery. Univariate correlation and multiple regression procedures were used to develop cognitive models of overall FCI performance across groups. The control model (R2 = .38) comprised (in order of entry) written arithmetic skills, delayed story recall, and simple visuomotor sequencing. The MCI model (R2 = .69) comprised written arithmetic skills, visuomotor sequencing and set alternation, and race. The AD model (R2 = .65) comprised written arithmetic skills, simple visuomotor sequencing, and immediate story recall. Written arithmetic skills (WRAT-3 Arithmetic) was the primary predictor across models, accounting for 27% (control model), 46% (AD model), and 55% (MCI model) of variance. Executive function and verbal memory were secondary model predictors. The results offer insight into the cognitive basis of financial capacity across the dementia spectrum of cognitive aging, MCI, and AD. (JINS, 2009, 15, 258–267.)
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- By Donald Addington, Jean Addington, Kelly Allott, Amanda Baker, Gregor Berger, Michael Berk, Max Birchwood, Warrick J. Brewer, Peter Burnett, Tyrone Cannon, Andrew Chanen, Philippe Conus, Barbara Cornblatt, Thomas Craig, Alex Fornito, David Fowler, Shona M. Francey, John Gleeson, Susy Harrigan, Meredith Harris, Leanne Hides, Christian G. Huber, Henry J. Jackson, Anthony F. Jorm, Eóin Killackey, Joachim Klosterkötter, Martin Lambert, Tim Lambert, Shon Lewis, Don Linszen, Dan Lubman, Nellie Lucas, Craig Macneil, Ashok K. Malla, Max Marshall, Louise K. McCutcheon, Patrick D. McGorry, Catharine McNab, Maria Michail, Anthony P. Morrison, Merete Nordentoft, Ross M. G. Norman, Keith H. Nuechterlein, Christos Pantelis, Lisa J. Phillips, Richie Poulton, Paddy Power, Jo Robinson, Frauke Schultze-Lutter, Jim van Os, José Luis Vázquez-Barquero, Dennis Velakoulis, Darryl Wade, Daniel Weinberger, Durk Wiersma, Stephen J. Wood, Annemarie Wright, Murat Yücel, Alison R. Yung, Robert B. Zipursky
- Edited by Henry J. Jackson, University of Melbourne, Patrick D. McGorry
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- Book:
- The Recognition and Management of Early Psychosis
- Published online:
- 10 August 2009
- Print publication:
- 19 February 2009, pp xi-xvi
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Sand Fiold: the Excavation of an Exceptional Cist in Orkney
- Magnar Dalland, John Barber, Stephen Carter, Ann Clarke, Dianne Dixon, Daphne Home Lorimer, Helen Kibble, Jacqueline I. McKinley, Ann Macsween, Coralie M. Mills, Alix H. Powers, Richard Tipping, Philippa Tomlinson, Paul Watson, Patricia Wiltshire
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- Journal:
- Proceedings of the Prehistoric Society / Volume 65 / 1999
- Published online by Cambridge University Press:
- 18 February 2014, pp. 373-413
- Print publication:
- 1999
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Sand quarrying in 1989 at Sand Fiold, Sandwick, in Orkney resulted in the accidental discovery of a rock-cut chamber containing a cist. Subsequent excavation revealed that this cist had a number of unusual features. The cist slabs had been fitted together exceptionally well and the completed cist was designed to be re-opened by the removal of a side slab. Within the chamber, access was provided to the opening side of the cist and a relieving structure was built over its capstone.
The cist contained cremation and inhumation burials that had been inserted on more than one occasion; as its builders intended. A collection of poorly preserved unburnt bone was found to comprise the remains of two individuals: a young adult and a foetus. Two collections of cremated bone, each derived from a single adult, were also present; one in a Food Vessel Urn, the second forming a pile on the floor and containing two burnt antler tines and two unburnt human teeth. The un-urned cremation deposit and the unburnt bones had been covered in mats of plant fibres derived from grass and sedge. The urn had been lined with basketry, also made from grass. Outside the cist, an exceptionally large collection of fuel ash slag (FAS), derived from a cremation pyre, had been deposited between the cist and the wall of the rock-cut chamber.
Radiocarbon dates indicate that the site and its contents had a long history. The FAS and the foetus skeleton date to 2900–2500 cal BC. Between 2200 and 1900 cal BC the urned cremation and young adult human bones were inserted and charcoal was deposited in the foundation slots for the back wall of the cist. The deposition of the un-urned cremation was dated to 1000–800 cal BC, some 900 years later, when the urn had already fallen over and broken. At this time, it is assumed that the urn was restored to an upright position and propped with stones, while the stone lid for the urn was reused in the foundation slot of the left-hand side of the cist. Reuse and refurbishment over two millennia seem evidenced in the results from this cist.
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