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1. Potential Sexual Transmission of Antifungal-Resistant Trichophyton indotineae

Author

Stephanie Spivack, Jeremy A.W. Gold, Shawn R. Lockhart, Priyanka Anand, Laura A.S. Quilter, Dallas J. Smith, Briana Bowen, Jane M. Gould, Ahmed Eltokhy, Ahmed Gamal, Mauricio Retuerto, Thomas S. McCormick, and Mahmoud A. Ghannoum

Subjects
tinea, fungi, Trichophyton indotineae, sexually transmitted infections, dermatophytes, dermatomycoses, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

We describe a case of tinea genitalis in an immunocompetent woman in Pennsylvania, USA. Infection was caused by Trichophyton indotineae potentially acquired through sexual contact. The fungus was resistant to terbinafine (first-line antifungal) but improved with itraconazole. Clinicians should be aware of T. indotineae as a potential cause of antifungal-resistant genital lesions.

Published
2024
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2. Fatal Fungicide-Associated Triazole-Resistant Aspergillus fumigatus Infection, Pennsylvania, USA

Author

Kennedy Bradley, Audrey Le-Mahajan, Beth Morris, Tiina Peritz, Tom Chiller, Kaitlin Forsberg, Natalie S. Nunnally, Shawn R. Lockhart, Jeremy A.W. Gold, and Jane M. Gould

Subjects
Fungi, antimicrobial resistance, respiratory infections, Aspergillus fumigatus, antifungal drug resistance, invasive mold infection, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

We report a fatal infection in a 65-year-old immunocompromised male patient caused by pan-triazole–resistant Aspergillus fumigatus containing a TR34/L98H genetic mutation linked to agricultural fungicide use. Clinical and environmental surveillance of triazole-resistant A. fumigatus is needed in the United States to prevent spread and guide healthcare and agricultural practices.

Published
2022
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4. Contributors

Author

Mark J. Abzug, Elisabeth E. Adderson, Aastha Agarwal, Allison L. Agwu, Lindsey Albenberg, Jonathan Albert, Kevin Alby, Grace M. Aldrovandi, Upton D. Allen, Gerardo Alvarez-Hernndez, Krow Ampofo, Evan J. Anderson, Grace D. Appiah, Monica I. Ardura, Stephen S. Arnon, Naomi E. Aronson, Ann M. Arvin, Shai Ashkenazi, Liat Ashkenazi-Hoffnung, Edwin J. Asturias, Kestutis Aukstuolis, Vahe Badalyan, Carol J. Baker, Karthik Balakrishnan, Elizabeth D. Barnett, Kirsten Bechtel, William E. Benitz, Rachel Berkovich, David M. Berman, Stephanie R. Bialek, Else M. Bijker, Matthew J. Bizzarro, Karen C. Bloch, Joseph A. Bocchini, Thomas G. Boyce, John S. Bradley, Denise F. Bratcher, Paula K. Braverman, Itzhak Brook, Kevin Edward Brown, Kristina P. Bryant, Andres F. Camacho-Gonzalez, Connie F. Caete-Gibas, Joseph B. Cantey, Paul Cantey, Cristina V. Cardemil, Mary T. Caserta, Luis A. Castagnini, Jessica R. Cataldi, Ellen Gould Chadwick, Rebecca J. Chancey, Cara C. Cherry, Silvia S. Chiang, Mary Choi, John C. Christenson, Susan E. Coffin, Amanda Cohn, Despina G. Contopoulos-Ioannidis, James H. Conway, Margaret M. Cortese, C. Buddy Creech, Jonathan D. Crews, Donna Curtis, Nigel Curtis, Lara A. Danziger-Isakov, Toni Darville, Gregory A. Dasch, Irini Daskalaki, H. Dele Davies, Fatimah S. Dawood, J. Christopher Day, M. Teresa de la Morena, Gregory P. DeMuri, Dickson D. Despommier, Daniel S. Dodson, Stephen J. Dolgner, Clinton Dunn, Jonathan Dyal, Kathryn M. Edwards, Morven S. Edwards, Dawn Z. Eichenfield, Lawrence F. Eichenfield, Dirk M. Elston, Beth Emerson, Leslie A. Enane, Moshe Ephros, Guliz Erdem, Marina E. Eremeeva, Douglas H. Esposito, Monica M. Farley, Anat R. Feingold, Kristina N. Feja, Adam Finn, Marc Fischer, Brian T. Fisher, Randall G. Fisher, Patricia Michele Flynn, Monique A. Foster, LeAnne M. Fox, Michael M. Frank, Douglas R. Fredrick, Robert W. Frenck, James Gaensbauer, Hayley A. Gans, Gregory M. Gauthier, Patrick Gavigan, Jeffrey S. Gerber, Yael Gernez, Francis Gigliotti, Mark A. Gilger, Carol A. Glaser, Jane M. Gould, James Graziano, Amanda M. Green, Michael Green, Daniel Griffin, Patricia M. Griffin, David C. Griffith, Piyush Gupta, Bruce J. Gutelius, Julie R. Gutman, Aron J. Hall, Rana F. Hamdy, Jin-Young Han, Lori K. Handy, Benjamin Hanisch, Marvin B. Harper, Aaron M. Harris, Christopher J. Harrison, David B. Haslam, Julia C. Haston, Sarah.J. Hawkes, Taylor Heald-Sargent, J. Owen Hendley, Adam L. Hersh, Joseph A. Hilinski, Susan L. Hills, David K. Hong, Peter J. Hotez, Katherine K. Hsu, Felicia Scaggs Huang, David A. Hunstad, W. Garrett Hunt, Loris Y. Hwang, Christelle M. Ilboudo, Preeti Jaggi, Sophonie Jean, Ravi Jhaveri, Kateina Jirk-Pomajbkov, Nadia A. Kadry, Mary L. Kamb, Ronak K. Kapadia, Ben Z. Katz, Sophie E. Katz, Ishminder Kaur, Gilbert J. Kersh, Muhammad Ali Khan, Ananta Khurana, David W. Kimberlin, Bruce Klein, Miwako Kobayashi, Larry K. Kociolek, Andrew Y. Koh, Karen L. Kotloff, Andrew T. Kroger, Matthew P. Kronman, Leah Lalor, Christine T. Lauren, Amy Leber, Eyal Leshem, David B. Lewis, Robyn A. Livingston, Eloisa Llata, Kevin Lloyd, Katrina Loh, Sarah S. Long, Benjamin A. Lopman, Yalda C. Lucero, Debra J. Lugo, Jorge Lujn-Zilbermann, Yvonne A. Maldonado, John J. Manaloor, Kalpana Manthiram, Stacey W. Martin, Roshni Mathew, Tony Mazzulli, Elizabeth J. McFarland, Kathleen A. McGann, Lucy A. McNamara, Debrah Meislich, H. Cody Meissner, Asuncion Mejias, Jussi Mertsola, Kevin Messacar, Mohammad Nael Mhaissen, Marian G. Michaels, Melissa B. Miller, Hilary Miller-Handley, Eric Mintz, Parvathi Mohan, Susan P. Montgomery, Jose G. Montoya, Anne C. Moorman, Pedro L. Moro, Anna-Barbara Moscicki, William J. Muller, Angela L. Myers, Simon Nadel, Jennifer Lynn Nayak, Michael Noel Neely, Karen P. Neil, Christina A. Nelson, Noele P. Nelson, Megin Nichols, William Nicholson, Amy Jo Nopper, Laura E. Norton, Theresa J. Ochoa, Liset Olarte, Timothy R. Onarecker, Walter A. Orenstein, Miguel ORyan, William R. Otto, Christopher P. Ouellette, Christopher D. Paddock, Debra L. Palazzi, Suresh Kumar Panuganti, Diane E. Pappas, Michal Paret, Daniel M. Pastula, Thomas F. Patterson, Brett W. Petersen, Mikael Petrosyan, Larry K. Pickering, Talia Pindyck, Swetha Pinninti, Laure F. Pittet, Paul J. Planet, Andrew J. Pollard, Klara M. Posfay-Barbe, Casper S. Poulsen, Susan M. Poutanen, Ann M. Powers, Nina Salinger Prasanphanich, Bobbi S. Pritt, Charles G. Prober, Neha Puar, Laura A.S. Quilter, Octavio Ramilo, Suchitra Rao, Adam J. Ratner, Sarah A. Rawstron, Jennifer S. Read, Ryan F. Relich, Megan E. Reller, Candice L. Robinson, Jos R. Romero, David A. Rosen, Shannon A. Ross, G. Ingrid J.G. Rours, Peter C. Rowe, Anne H. Rowley, Lorry G. Rubin, Edward T. Ryan, Alexandra Sacharok, Thomas J. Sandora, Sarah G.H. Sapp, Kabir Sardana, Jason B. Sauberan, Joshua K. Schaffzin, Sarah Schillie, Jennifer E. Schuster, Kevin L. Schwartz, Bethany K. Sederdahl, Jose Serpa-Alvarez, Kara N. Shah, Samir S. Shah, Nader Shaikh, Andi L. Shane, Eugene D. Shapiro, Jana Shaw, Avinash K. Shetty, Timothy R. Shope, Linda M. Dairiki Shortliffe, Stanford T. Shulman, Gail F. Shust, George Kelly Siberry, Jane D. Siegel, Robert David Siegel, Kari A. Simonsen, Upinder Singh, Christiana Smith, Lauren L. Smith, Eunkyung Song, Emily Souder, Paul Spearman, Joseph W. St. Geme, Mary Allen Staat, J. Erin Staples, Jeffrey R. Starke, Victoria A. Statler, William J. Steinbach, Christen Rune Stensvold, Erin K. Stokes, Bradley P. Stoner, Gregory A. Storch, Anne Straily, Kathleen E. Sullivan, Douglas S. Swanson, Robert R. Tanz, Gillian Taormina, Jacqueline E. Tate, Jeanette Taveras, Marc Tebruegge, Eyasu H. Teshale, George R. Thompson, Robert Thompson-Stone, Isaac Thomsen, Richard B. Thomson, Emily A. Thorell, Vivian Tien, Nicole H. Tobin, Philip Toltzis, James Treat, Stephanie B. Troy, Russell B. Van Dvke, Louise Elaine Vaz, Vini Vijayan, Jennifer Vodzak, Thor A. Wagner, Ellen R. Wald, Rebecca Wallihan, Huanyu Wang, Zoon Wangu, Matthew Washam, Valerie Waters, Joshua R. Watson, Jill E. Weatherhead, Geoffrey A. Weinberg, Mark K. Weng, Nathan P. Wiederhold, Harold C. Wiesenfeld, Cydni Williams, John V. Williams, Rodney E. Willoughby, Robert R. Wittler, James B. Wood, Charles Reece Woods, Kimberly A. Workowski, Terry W. Wright, Hsi-Yang Wu, Huan Xu, Pablo Yagupsky, Jumi Yi, Jonathan Yoder, Edward J. Young, Andrea L. Zaenglein, Petra Zimmermann, and Wenjing Zong

Published
2023
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5. A Collaborative Public Health and Veterinary Facility Approach to an NDM-5 Escherichia coli Outbreak

Author

Jane M. Gould, Stephen D. Cole, Matthew J. Ryan, Susy Rettig, Kristin Privette, Tiina Peritz, Susan Coffin, Betsy Schroeder, Donna Oakley, and Shelley C. Rankin

Subjects
Microbiology (medical), Veterinary medicine, medicine.medical_specialty, Epidemiology, business.industry, Transmission (medicine), media_common.quotation_subject, Public health, Disease cluster, Occupational safety and health, Infectious Diseases, Hygiene, Health care, Medicine, Infection control, business, Respiratory care, media_common
Abstract

Background: Carbapenem-resistant Enterobacteriaceae (CRE) are an important cause of healthcare-associated infections (HAIs) in human hospitals. The Philadelphia Department of Public Health (PDPH) made CRE reportable in April 2018. In May 2019, the Matthew J. Ryan Veterinary Hospital (MJRVH) reported an NDM-5 Escherichia coli cluster in companion animals to the PDPH. In total, 15 infected animals (14 dogs and 1 cat) were reported between July 2018 and June 2019, with no new infections after June 2019. Limited literature is available on the prevalence of CRE in companion animals, and recommendations for dealing with CRE infections currently target human healthcare settings. Methods: A collaborative containment response included assessing interspecies transmission to veterinary staff and a comprehensive evaluation of the infection control program at MJRVH. MJRVH notified all owners of affected animals verbally and via notification letters with PDPH recommendations for CRE colonization screening of high-risk individuals. CRE screening of exposed high-risk employees was conducted by the University of Pennsylvania Occupational Health service and PDPH. Human rectal swabs were analyzed at the Antibiotic Resistance Laboratory Network (ARLN) Maryland Laboratory. PDPH were invited to conduct an onsite infection control assessment and to suggest improvements. Results: No pet owners self-identified in high-risk groups to be screened. In total, 10 high-risk staff were screened, and no colonized individuals were detected. Recommendations made by the PDPH to MJRVH included improvement of infection prevention and control policies (eg, consolidation of the infection control manual and identification of lead staff member), improvement in hand hygiene (HH) compliance (eg, increasing amount of HH supplies), improvement of environment of care (eg, decluttering and evaluation of mulched animal relief area), and improvement of respiratory care processes (eg, standardization of care policies). MJRVH made substantial improvements across recommendation areas including revision of infection control manual, creation of a full-time infection preventionist position, individual alcohol hand sanitizers for patient cages, and environmental decluttering and decontamination. PDPH and MJRVH maintained frequent communication about infection control improvements. Conclusions: No positive transmission to high-risk staff members suggest that, like in human healthcare facilities, transmission of CRE to caretakers may not be a common event. Stronger communication and collaboration is required from Departments of Public Health (DPH) to the veterinary profession regarding the reporting requirements of emerging pathogens such as CRE. Veterinary facilities should view DPH as a valuable resource for recommendations to fill in gaps that exist in infection control “best practices,” particularly for novel pathogens in veterinary settings.Funding: NoneDisclosures: Jane M. Gould reports that her spouse receives salary from Incyte.

Published
2020
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6. Hospital-Based Playrooms, Classrooms, and Pet Therapy

Author

Jane M. Gould

Subjects
medicine.medical_specialty, Pet therapy, business.industry, Medicine, Medical physics, Hospital based, business
Abstract

A unique feature of most pediatric healthcare facilities is that they provide opportunities for both inpatients and outpatients to participate in play with developmentally appropriate toys during their medical care. Reasons for play in hospitalized pediatric patients may include providing mechanisms to educate children about their particular medical conditions, providing stress reduction during frightening procedures, assisting in the development of coping strategies, and attempting to maintain a sense of normalcy during long hospitalizations. Although toys and playroom environments provide a vital psychosocial and quality-of-life function, however, they are also known to contribute to the transmission of infectious agents. This chapter provides guidance on minimizing transmission of pathogens in hospital-based playrooms and classrooms: pathogens that are commonly found in pediatric healthcare facilities. This chapter also discusses the transmission challenges with pet therapy programs for children, and suggests approaches for safe implementation of these programs. Sample policies are included.

Published
2019
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7. Clinical Correlates of Surveillance Events Detected by National Healthcare Safety Network Pneumonia and Lower Respiratory Infection Definitions—Pennsylvania, 2011–2012

Author

Sydney Hubbard, Genevieve L. Buser, Debra Hess, Judith O'donnell, Isaac See, Julia Chang, Jane M. Gould, Pamela Rohrbach, Patricia Hennessey, David A. Pegues, Shelley S. Magill, Andrea Kiernan, Mary Jo Bellush, Debra A Smeltz, Jeffrey R. Miller, Nicole Gualandi, and Susan E. Coffin

Subjects
Adult, Microbiology (medical), medicine.medical_specialty, Epidemiology, medicine.medical_treatment, 030501 epidemiology, Article, 03 medical and health sciences, 0302 clinical medicine, Health care, Pneumonia, Bacterial, medicine, Humans, 030212 general & internal medicine, Medical diagnosis, Child, Lower respiratory infection, Intensive care medicine, Respiratory Tract Infections, Aged, Retrospective Studies, Aged, 80 and over, Mechanical ventilation, Cross Infection, Respiratory tract infections, business.industry, Medical record, Infant, Newborn, Infant, Pneumonia, Ventilator-Associated, Retrospective cohort study, Pneumonia, Middle Aged, Pennsylvania, medicine.disease, Community-Acquired Infections, Infectious Diseases, Child, Preschool, Population Surveillance, Emergency medicine, 0305 other medical science, business
Abstract

OBJECTIVETo determine the clinical diagnoses associated with the National Healthcare Safety Network (NHSN) pneumonia (PNEU) or lower respiratory infection (LRI) surveillance eventsDESIGNRetrospective chart reviewSETTINGA convenience sample of 8 acute-care hospitals in PennsylvaniaPATIENTSAll patients hospitalized during 2011–2012METHODSMedical records were reviewed from a random sample of patients reported to the NHSN to have PNEU or LRI, excluding adults with ventilator-associated PNEU. Documented clinical diagnoses corresponding temporally to the PNEU and LRI events were recorded.RESULTSWe reviewed 250 (30%) of 838 eligible PNEU and LRI events reported to the NHSN; 29 reported events (12%) fulfilled neither PNEU nor LRI case criteria. Differences interpreting radiology reports accounted for most misclassifications. Of 81 PNEU events in adults not on mechanical ventilation, 84% had clinician-diagnosed pneumonia; of these, 25% were attributed to aspiration. Of 43 adult LRI, 88% were in mechanically ventilated patients and 35% had no corresponding clinical diagnosis (infectious or noninfectious) documented at the time of LRI. Of 36 pediatric PNEU events, 72% were ventilator associated, and 70% corresponded to a clinical pneumonia diagnosis. Of 61 pediatric LRI patients, 84% were mechanically ventilated and 21% had no corresponding clinical diagnosis documented.CONCLUSIONSIn adults not on mechanical ventilation and in children, most NHSN-defined PNEU events corresponded with compatible clinical conditions documented in the medical record. In contrast, NHSN LRI events often did not. As a result, substantial modifications to the LRI definitions were implemented in 2015.Infect Control Hosp Epidemiol 2016;37:818–824

Published
2016
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8. 1441. Using Carbapenem Resistance Levels to Discriminate Between Carbapenemase Producing and Non-Carbapenemase Producing Carbapenem Resistant Enterobacteriaceae

Author

William J Koehne, Tiina Peritz, Kristin Privette, and Jane M. Gould

Subjects
Carbapenem, Imipenem, biology, business.industry, Klebsiella pneumoniae, Carbapenem-resistant enterobacteriaceae, biology.organism_classification, Meropenem, Microbiology, chemistry.chemical_compound, AcademicSubjects/MED00290, Infectious Diseases, Oncology, chemistry, Poster Abstracts, medicine, Doripenem, business, Enterobacter cloacae, Ertapenem, medicine.drug
Abstract

Background Carbapenem-resistant Enterobacteriaceae (CRE) are a growing threat globally. Many CRE organisms carry plasmids that produce a carbapenemase enzyme (CP-CRE). Early detection of CP-CRE and aggressive infection prevention and control (IPC) measures are necessary to reduce transmission of resistant organisms and their plasmids. Many hospital laboratories do not test CRE for carbapenemase production. In Apr ‘18, the Philadelphia Department for Public Health (PDPH) established mandatory CRE reporting including isolate submission for mechanism testing at public health laboratories. Methods We analyzed trends of carbapenem resistance in CP and non-CP-CRE. We calculated sensitivity (Sen), specificity (Spe), positive and negative predictive values (PPV, NPV) at each level of carbapenem resistance to develop a predictive model with goal of effectively discriminating CP and non-CP CRE. ROC curves were plotted. Results From June,’18-Feb,’20, 351 CRE had genetic mechanism testing. 192 (54.7%) were Klebsiella pneumoniae, 53 (15.1%) were Enterobacter cloacae, 52 (14.8%) were E. coli, and the remaining 54 (15.4%) other Enterobacteriaceae.186 (53.0%) had a recorded minimum inhibitory concentration (MIC) for ertapenem, 191 (54.4%) for meropenem, 116 (33.0%) for imipenem, and 9 (2.6%) for doripenem. Doripenem was not further analyzed. The odds of being CP-CRE increased with increasing MIC. One standard dilution increase in MIC was associated with the following odds ratios (OR) of being CP-CRE: ertapenem OR 1.43 (95% CI: 1.11–1.83), imipenem OR 2.52 (95% CI: 1.7–3.793), meropenem, OR 2.20 (95% CI: 1.72–2.81). For each carbapenem, we calculated Sen, Spe, PPV, and NPV values for five MIC cut points; 0.5, 1, 2, 4, and 8 ug/ml, non-CP CRE defined as ≤ MIC cut point, CP-CRE defined as > cut point. Figure 1. ROC Curves Table 1. Sensitivity, Specificity, PPV, NPV of MIC Cut Points Conclusion There were no MIC cut points that performed well in both Sen and Spe, however, for the purposes of IPC, correctly classifying CP CRE (Sen) is more important than correctly classifying non-CP CRE (Spe). MIC cut points that performed best were imipenem MIC of 1 ug/ml and meropenem MIC of 1 ug/ml, with Sen 98%, 94% respectively, PPV 85%, 84% respectively and NPV 88%, 76% respectively. When further testing is not available, MIC cut points may be used to infer CP production. Disclosures All Authors: No reported disclosures

Published
2020
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9. Healthcare-Associated Infections

Author

Jane M. Gould and Susan E. Coffin

Subjects
Healthcare associated infections, medicine.medical_specialty, business.industry, Medicine, business, Intensive care medicine
Published
2018
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10. Contributors

Author

Mark J. Abzug, Elisabeth E. Adderson, Allison L. Agwu, Kevin Alby, Grace M. Aldrovandi, Upton D. Allen, Gerardo Alvarez-Hernández, Krow Ampofo, Evan J. Anderson, Margot Anderson, Stella Antonara, Monica I. Ardura, Paul M. Arguin, John C. Arnold, Naomi E. Aronson, Ann M. Arvin, Shai Ashkenazi, Edwin J. Asturias, Vahe Badalyan, Carol J. Baker, Karthik Balakrishnan, Brittany S. Barros, William J. Barson, Daniel G. Bausch, Kirsten Bechtel, Daniel K. Benjamin, David M. Berman, David A. Blanco, Karen C. Bloch, Margaret J. Blythe, Joseph A. Bocchini, Anna Bowen, William R. Bowie, Thomas G. Boyce, John S. Bradley, Michael T. Brady, Denise F. Bratcher, Paula K. Braverman, Joseph Bresee, Itzhak Brook, Kevin E. Brown, Kristina Bryant, E. Stephen Buescher, Jane L. Burns, Carrie L. Byington, Andres F. Camacho-Gonzalez, Paul Cantey, Bryan D. Carter, Mary T. Caserta, Luis A. Castagnini, Chiara Cerini, Ellen Gould Chadwick, Silvia S. Chiang, John C. Christenson, Susan E. Coffin, Melissa G. Collier, Jennifer P. Collins, Laurie S. Conklin, Beverly L. Connelly, Despina Contopoulos-Ioannidis, James H. Conway, Margaret M. Cortese, Elaine G. Cox, C. Buddy Creech, Jonathan D. Crews, Dennis J. Cunningham, Nigel Curtis, Natalie J.M. Dailey, Lara A. Danziger-Isakov, Toni Darville, Gregory A. Dasch, Irini Daskalaki, Robert S. Daum, Michael Davenport, H. Dele Davies, Fatimah S. Dawood, J. Christopher Day, Maite de la Morena, Gail J. Demmler-Harrison, Gregory P. DeMuri, Dickson D. Despommier, Karen A. Diefenbach, Kathryn M. Edwards, Morven S. Edwards, Lawrence F. Eichenfield, Dirk M. Elston, Beth Emerson, Moshe Ephros, Guliz Erdem, Marina E. Eremeeva, Jessica E. Ericson, Douglas H. Esposito, Monica M. Farley, Anat R. Feingold, Kristina N. Feja, Adam Finn, Marc Fischer, Patricia M. Flynn, LeAnne M. Fox, Michael M. Frank, Douglas R. Fredrick, Robert W. Frenck, Sheila Fallon Friedlander, Hayley A. Gans, Gregory M. Gauthier, Jeffrey S. Gerber, Francis Gigliotti, Mark A. Gilger, Carol A. Glaser, Amanda F. Goddard, Benjamin D. Gold, Jane M. Gould, Michael Green, David Greenberg, Tanya Greywal, Daniel Griffin, Patricia M. Griffin, Alexei A. Grom, Kathleen Gutierrez, Julie Gutman, Judith A. Guzman-Cottrill, Aron J. Hall, Jin-Young Han, Marvin B. Harper, Julie R. Harris, Christopher J. Harrison, David B. Haslam, Sarah J. Hawkes, J. Owen Hendley, Marion C.W. Henry, Joseph A. Hilinski, Susan L. Hills, Scott D. Holmberg, Deborah Holtzman, David K. Hong, Peter J. Hotez, Katherine K. Hsu, David A. Hunstad, Loris Y. Hwang, Mary Anne Jackson, Richard F. Jacobs, Ravi Jhaveri, Kateřina Jirků-Pomajbíková, Jeffrey L. Jones, Mahima Karki, M. Gary Karlowicz, Ben Z. Katz, Ishminder Kaur, Gilbert J. Kersh, Jay S. Keystone, Muhammad Ali Khan, David W. Kimberlin, Martin B. Kleiman, Bruce S. Klein, Karl Klontz, Barbara Knust, Andrew Y. Koh, E. Kent Korgenski, Paul Krogstad, Preeta Krishnan Kutty, Christine T. Lauren, Hillary S. Lawrence, Amy Leber, Grace M. Lee, Eugene Leibovitz, Eyal Leshem, Stéphanie Levasseur, David B. Lewis, Robyn A. Livingston, Eloisa Llata, Sarah S. Long, Ben A. Lopman, Yalda C. Lucero, Jorge Luján-Zilbermann, Katherine Luzuriaga, Noni E. MacDonald, Yvonne A. Maldonado, John Manaloor, Chitra S. Mani, Kalpana Manthiram, Gary S. Marshall, Stacey W. Martin, Almea Matanock, Catalina Matiz, Alison C. Mawle, Tony Mazzulli, Kathleen A. McGann, Kenneth McIntosh, Lucy A. McNamara, Michal Meir, Debrah Meislich, H. Cody Meissner, Elissa Meites, Asunción Mejías, Jussi Mertsola, Kevin Messacar, Mohammed Nael Mhaissen, Marian G. Michaels, Melissa B. Miller, Eric D. Mintz, John F. Modlin, Parvathi Mohan, Susan P. Montgomery, José G. Montoya, Pedro L. Moro, Anna-Barbara Moscicki, R. Lawrence Moss, Angela L. Myers, Simon Nadel, Michael N. Neely, Karen P. Neil, Joanna Nelson, Noele P. Nelson, William L. Nicholson, Victor Nizet, Amy Jo Nopper, Theresa J. Ochoa, Walter A. Orenstein, Miguel O'Ryan, Christopher D. Paddock, Harpreet Pall, Suresh Kumar Panuganti, Diane E. Pappas, Robert F. Pass, Thomas F. Patterson, Monica E. Patton, Stephen I. Pelton, Brett W. Petersen, Larry K. Pickering, Swetha Pinninti, Paul J. Planet, Andrew J. Pollard, Klara M. Posfay-Barbe, Casper S. Poulsen, Susan M. Poutanen, Ann M. Powers, Charles G. Prober, Octavio Ramilo, Shawn J. Rangel, Suchitra Rao, Sarah A. Rawstron, Jennifer S. Read, Michael D. Reed, Ryan F. Relich, Megan E. Reller, Neil Rellosa, Katherine A. Rempe, Melissa A. Reyes, Samuel E. Rice-Townsend, Frank O. Richards, José R. Romero, David A. Rosen, Christina A. Rostad, G. Ingrid J.G. Rours, Janell A. Routh, Anne H. Rowley, Lorry G. Rubin, Edward T. Ryan, Lisa Saiman, Julia S. Sammons, Laura Sass, Jason B. Sauberan, Sarah Schillie, Grant S. Schulert, Jennifer E. Schuster, Kevin L. Schwartz, Bethany K. Sederdahl, Jose A. Serpa, Kara N. Shah, Samir S. Shah, Andi L. Shane, Eugene D. Shapiro, Jana Shaw, Avinash K. Shetty, Linda M. Dairiki, George Kelly Siberry, Jane D. Siegel, Robert David Siegel, Kari A. Simonsen, Nalini Singh, Upinder Singh, P. Brian Smith, John D. Snyder, Eunkyung Song, Jennifer L. Sorrell, Emily Souder, Joseph W. St. Geme, Mary Allen Staat, J. Erin Staples, Jeffrey R. Starke, William J. Steinbach, Christen R. Stensvold, Bradley P. Stoner, Raymond A. Strikas, Jonathan B. Strober, Paul K. Sue, Deanna A. Sutton, Douglas Swanson, Jacqueline E. Tate, Marc Tebruegge, Eyasu H. Teshale, Amelia B. Thompson, George R. Thompson, Robert Thompson-Stone, Richard B. Thomson, Emily A. Thorell, Nicole H. Tobin, Philip Toltzis, James Treat, Stephanie B. Troy, Russell B. Van, Louise Elaine Vaz, Jennifer Vodzak, Ellen R. Wald, Rebecca Wallihan, Zoon Wangu, Matthew Washam, Joshua R. Watson, Rachel L. Wattier, Geoffrey A. Weinberg, A. Clinton White, Harold C. Wiesenfeld, John V. Williams, Rodney E. Willoughby, Sarah L. Wingerter, Robert R. Wittler, Karen K. Wong, Kimberly A. Workowski, Terry W. Wright, Pablo Yagupsky, Catherine Yen, Jumi Yi, Jonathan S. Yoder, Edward J. Young, Andrea L. Zaenglein, and Kanecia Zimmerman

Published
2018
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12. Tuberculosis and Pregnancy-Maternal, Fetal, and Neonatal Considerations

Author

Stephen C. Aronoff and Jane M. Gould

Subjects
Microbiology (medical), Male, medicine.medical_specialty, Tuberculosis, Physiology, Developing country, 03 medical and health sciences, 0302 clinical medicine, Tuberculosis diagnosis, Infectious Epidemiology, Pregnancy, Genetics, Medicine, Maternal fetal, Humans, 030212 general & internal medicine, Pregnancy Complications, Infectious, Intensive care medicine, Fetus, 030219 obstetrics & reproductive medicine, General Immunology and Microbiology, Ecology, business.industry, Transmission (medicine), Infant, Newborn, Cell Biology, medicine.disease, Infectious Disease Transmission, Vertical, Infectious Diseases, Immunology, Paternal Exposure, Female, business
Abstract

The issue of tuberculosis during pregnancy is not simply a historical inquiry but rather an increasingly familiar clinical problem facing industrial nations as well as the developing countries of the world. This review focuses on the maternal aspects of tuberculous infection, as well as transmission to the fetus and newborn.

Published
2017

13. Herpes Simplex Virus Infection in Young Infants During 2 Decades of Empiric Acyclovir Therapy

Author

Jennifer Vodzak, Irini Daskalaki, Sarah S. Long, Jane M. Gould, and Tamara E. Pool

Subjects
Male, Microbiology (medical), Herpes simplex virus infection, Pediatrics, medicine.medical_specialty, Virus Cultivation, viruses, Acyclovir, Antiviral Agents, Polymerase Chain Reaction, Young infants, Institutional strategy, Meningoencephalitis, medicine, Humans, Simplexvirus, Aciclovir, Stomatitis, Cerebrospinal Fluid, business.industry, Acyclic nucleoside, Infant, Newborn, Mouth Mucosa, Infant, Herpes Simplex, medicine.disease, Stomatitis, Herpetic, Infectious Diseases, Pediatrics, Perinatology and Child Health, Immunology, Female, Viral disease, business, medicine.drug
Abstract

To describe the clinical presentation of HSV-infected young infants and to seek distinctive features that could permit a targeted approach to empiric use of acyclovir.Case study of neonatal HSV during a 22-year period of an institutional strategy of consistent use of acyclovir empirically in all infants with onset of an illness at ≤ 21 days of age for which antibiotics were given empirically. Multiple sources were used to optimize HSV case data, and to estimate the rate of HSV infection in empirically treated infants.A total of 32 infants with perinatally acquired HSV infection were identified. All received acyclovir empirically at admission. At presentation, 50% of infants had only nonspecific complaints, which was fever in 75%. After testing, 75% of infants with HSV had central nervous system (CNS) infection, including 40% who presented with mucocutaneous lesions, 83% with seizures, and 94% with nonspecific complaints. Cerebrospinal fluid (CSF) polymerase chain reaction confirmed CNS infection in 16 of 22 (73%) patients tested. Cultures of mucocutaneous lesion yielded HSV in 8 of 10 cases, but culture of CSF was negative in all 26 cases tested, and screening cultures of unaffected mucosal sites were the only HSV-confirmatory test in a single patient. Laboratory and CSF findings were not distinctive in patients with HSV. Age of ≤ 21 days at onset of symptoms captured 90% of all infants with HSV and 94% of those with nonspecific complaints. An estimated 1.3% of empirically treated patients had HSV infection.Early manifestations of perinatally acquired HSV are frequently nonspecific, yet CNS infection is common. Empiric acyclovir strategy narrowly restricted to infants with onset of illness at ≤ 21 days of age, who would receive antibiotics empirically, captured 90% of HSV cases and anticipated a rate of HSV CNS infection similar to that of bacterial meningitis.

Published
2011
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14. Otitis Media

Author

Jane M. Gould and Paul S. Matz

Subjects
03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, Pediatrics, Perinatology and Child Health, 030212 general & internal medicine
Published
2010
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16. Public Health Department Contact Investigation and Directly Observed Prophylactic Therapy Enhance Completion of Latent Tuberculosis Infection (LTBI) Therapy in Children Compared with Adults

Author

Emily Souder, Jennifer Vodzak, Jane M. Gould, Sarah S. Long, and Christina Dogbey

Subjects
medicine.medical_specialty, Latent tuberculosis, business.industry, 030503 health policy & services, Public health, medicine.disease, Surgery, 03 medical and health sciences, 0302 clinical medicine, Infectious Diseases, Oncology, Medicine, 030212 general & internal medicine, 0305 other medical science, business, Intensive care medicine, Contact Investigation
Published
2016
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17. Isolation precautions for visitors

Author

Tara N. Palmore, Gonzalo Bearman, David J. Weber, Surbhi Leekha, L. Silvia Munoz-Price, Timothy L. Wiemken, Mark E. Rupp, Jane M. Gould, David B. Banach, and Daniel J. Morgan

Subjects
Microbiology (medical), medicine.medical_specialty, History, Epidemiology, MEDLINE, Masks, Visitors to Patients, Hospitals, Disease Outbreaks, Patient Isolation, Infectious Diseases, Isolation precautions, Family medicine, medicine, Disease Transmission, Infectious, Infection control, Humans, Hand Hygiene, Hospital epidemiology, Disease transmission, Patient isolation
Abstract

Infection Control & Hospital Epidemiology / FirstView Article / April 2015, pp 1 12 DOI: 10.1017/ice.2015.67, Published online: 10 April 2015 Link to this article: http://journals.cambridge.org/abstract_S0899823X15000677 How to cite this article: L. Silvia Munoz-Price, David B. Banach, Gonzalo Bearman, Jane M. Gould, Surbhi Leekha, Daniel J. Morgan, Tara N. Palmore, Mark E. Rupp, David J. Weber and Timothy L. Wiemken Isolation Precautions for Visitors. Infection Control & Hospital Epidemiology, Available on CJO 2015 doi:10.1017/ice.2015.67 Request Permissions : Click here

Published
2015

18. Phase variable desialylation of host proteins that bind to Streptococcus pneumoniae in vivo and protect the airway

Author

Deborah Bae, Claudine E. Fasching, Samantha J. King, Karen R. Hippe, Robin T. Cline, Jeffrey N. Weiser, Scott N. Peterson, Jane M. Gould, and Edward N. Janoff

Subjects
biology, Microarray analysis techniques, Secretory component, Lactoferrin, medicine.disease_cause, medicine.disease, Microbiology, Phenotype, In vivo, Streptococcus pneumoniae, Pneumococcal pneumonia, biology.protein, medicine, Molecular Biology, Neuraminidase
Abstract

Most clinical isolates of Streptococcus pneumoniae consist of heterogeneous populations of at least two colony phenotypes, opaque and transparent, selected for in the bloodstream and nasopharynx, respectively. Microarray analysis revealed 24 orfs that demonstrated differences in expression greater than twofold between variants of independent strains. Twenty-one of these showed increased expression in the transparent variants, including 11 predicted to be involved in sugar metabolism. A single genomic region contains seven of these loci including the gene that encodes the neuraminidase, NanA. In contrast to previous studies, there was no contribution of NanA to adherence of S. pneumoniae to epithelial cells or colonization in an animal model. However, we observed NanA-dependent desialylation of human airway components that bind to the organism and may mediate bacterial clearance. Targets of desialylation included human lactoferrin, secretory component, and IgA2 that were shown to be present on the surface of the pneumococcus in vivo during pneumococcal pneumonia. The efficiency of desialylation was increased in the transparent variants and enhanced for host proteins binding to the surface of S. pneumoniae. Because deglycosylation affects the function of many host proteins, NanA may contribute to a protease-independent mechanism to modify bound targets and facilitate enhanced survival of the bacterium.

Published
2004
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19. Rapid Multiplex PCR Gastrointestinal Panel Enhances Pathogen Identification and Can Improve Hospital Infection Prevention Practices in Pediatric Patients with Diarrhea

Author

Sarah S. Long, Jane M. Gould, Michael Heard, Ishminder Kaur, Jennifer Vodzak, and Alan T. Evangelista

Subjects
medicine.medical_specialty, business.industry, Virology, law.invention, Pathogenic organism, Diarrhea, Infectious Diseases, Oncology, law, Multiplex polymerase chain reaction, Infection control, Medicine, Identification (biology), medicine.symptom, business, Intensive care medicine, Pathogen, Polymerase chain reaction
Published
2015
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20. The Inhibitory Effect of C‐Reactive Protein on Bacterial Phosphorylcholine Platelet‐Activating Factor Receptor–Mediated Adherence Is Blocked by Surfactant

Author

Jane M. Gould and Jeffrey N. Weiser

Subjects
Phosphorylcholine, Blotting, Western, Receptors, Cell Surface, Platelet Membrane Glycoproteins, Biology, CHOP, medicine.disease_cause, Bacterial Adhesion, Receptors, G-Protein-Coupled, Haemophilus influenzae, Microbiology, chemistry.chemical_compound, Nasopharynx, hemic and lymphatic diseases, Streptococcus pneumoniae, Tumor Cells, Cultured, medicine, Humans, Immunology and Allergy, Receptor, Platelet-activating factor, C-reactive protein, Pulmonary Surfactants, Immunohistochemistry, C-Reactive Protein, Infectious Diseases, chemistry, biology.protein, Platelet-activating factor receptor
Abstract

Numerous major bacterial pathogens in the human respiratory tract, including Streptococcus pneumoniae and Haemophilus influenzae, express cell-surface phosphorylcholine (ChoP), a ligand for the receptor for platelet-activating factor (rPAF). ChoP is also bound by C-reactive protein (CRP), which, in the presence of complement, may be bactericidal. This study found that CRP can block the attachment of bacteria expressing cell-surface ChoP to host cells. Concentrations of CRP equivalent to those on the mucosal surface of the human airway blocked most adherence of both S. pneumoniae and H. influenzae to human pharyngeal epithelial cells. ChoP-mediated adherence was also reduced in the presence of an rPAF antagonist. The antiadhesive effects of the rPAF antagonist and CRP were not additive, suggesting that CRP activity is specific to the area of adherence mediated by the receptor. The binding of CRP to ChoP and the effect of CRP on adherence were inhibited by human surfactant (primarily ChoP). The antiadhesive effect of CRP may be diminished in the terminal airway, where surfactant is abundant.

Published
2002
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22. Contributors

Author

Elisabeth E. Adderson, Aarti Agarwal, Grace M. Aldrovandi, Upton D. Allen, Manuel R. Amieva, Krow Ampofo, Alicia D. Anderson, Margot Anderson, Paul M. Arguin, John C. Arnold, Ann M. Arvin, Shai Ashkenazi, Carol J. Baker, William J. Barson, Daniel G. Bausch, Kirsten Bechtel, Daniel K. Benjamin, Frank E. Berkowitz, Margaret J. Blythe, Joseph A. Bocchini, Michael Boeckh, Anna Bowen, William R. Bowie, Thomas G. Boyce, John S. Bradley, Michael T. Brady, Denise F. Bratcher, Paula K. Braverman, Caroline Breese Hall, Joseph S. Bresee, Itzhak Brook, Kristina Bryant, E. Stephen Buescher, Jane L. Burns, Gale R. Burstein, Carrie L. Byington, Kathy K. Byrd, Michael Cappello, Bryan D. Carter, Emily J. Cartwright, Mary T. Caserta, Chiara Cerini, Ellen Gould Chadwick, Beth Cheesebrough, P. Joan Chesney, John C. Christenson, Thomas G. Cleary, Susan E. Coffin, Laura M. Conklin, Laurie S. Conklin, Beverly L. Connelly, Despina Contopoulos-Ioannidis, James H. Conway, Margaret M. Cortese, C. Michael Cotten, Elaine Cox, Maryanne E. Crockett, James E. Crowe, Nigel Curtis, Dennis J. Cunningham, Linda Marie Dairiki Shortliffe, Toni Darville, Gregory A. Dasch, Irini Daskalaki, Robert S. Daum, Fatimah S. Dawood, Gail J. Demmler, Dickson D. Despommier, Karen A. Diefenbach, Christopher C. Dvorak, Kathryn M. Edwards, Morven S. Edwards, Lawrence F. Eichenfield, Dirk M. Elston, Janet A. Englund, Veronique Erard, Marina E. Eremeeva, Anat R. Feingold, Adam Finn, Anthony E. Fiore, Marc Fischer, Sarah J. Fitch, Patricia M. Flynn, LeAnne M. Fox, Michael M. Frank, Douglas R. Fredrick, Sheila Fallon Friedlander, Hayley A. Gans, Carla G. Garcia, Maria C. Garzon, Jeffrey S. Gerber, Michael D. Geschwind, Laura B. Gieraltowski, Francis Gigliotti, Peter H. Gilligan, Carol Glaser, Benjamin D. Gold, Brahm Goldstein, Jane M. Gould, Michael Green, David Greenberg, Patricia M. Griffin, Alexei A. Grom, Kathleen Gutierrez, Judith A. Guzman-Cottrill, Aron J. Hall, Marvin B. Harper, Christopher J. Harrison, David B. Haslam, Sarah J. Hawkes, Edward B. Hayes, Rohan Hazra, Sara Jane Heilig, J. Owen Hendley, Marion C.W. Henry, Joseph A. Hilinski, Scott D. Holmberg, Deborah Holtzman, Peter J. Hotez, Katherine K. Hsu, Dale J. Hu, Loris Y. Hwang, David Y. Hyun, Mary Anne Jackson, Richard F. Jacobs, Jeffrey L. Jones, Saleem Kamili, M. Gary Karlowicz, Ben Z. Katz, Gilbert J. Kersh, Laura M. Kester, Jay S. Keystone, David W. Kimberlin, Martin B. Kleiman, Mark W. Kline, Andrew Y. Koh, Andreas Konstantopoulos, Katalin I. Koranyi, E. Kent Korgenski, Andrew T. Kroger, Paul Krogstad, Christine T. Lauren, Hillary S. Lawrence, Eugene Leibovitz, Stéphanie Levasseur, David B. Lewis, Jay M. Lieberman, Jen-Jane Liu, Robyn A. Livingston, Eloisa Llata, Anagha R. Loharikar, Sarah S. Long, Ben A. Lopman, Bennett Lorber, Donald E. Low, Yalda C. Lucero, Jorge Luján-Zilbermann, Katherine Luzuriaga, Noni E. MacDonald, Adam MacNeil, Yvonne A. Maldonado, Chitra S. Mani, Mario J. Marcon, Gary S. Marshall, Stacey W. Martin, Catalina Matiz, Alison C. Mawle, Tony Mazzulli, George H. McCracken, Matthew B. McDonald, Robert S. McGregor, Kenneth McIntosh, Meredith McMorrow, Candice McNeil, Jennifer H. McQuiston, Debrah Meislich, H. Cody Meissner, Asunción Mejías, Manoj P. Menon, Jussi Mertsola, Marian G. Michaels, Melissa B. Miller, Eric D. Mintz, John F. Modlin, Parvathi Mohan, Susan P. Montgomery, Jose G. Montoya, Zack S. Moore, Maite de la Morena, Pedro L. Moro, Anna-Barbara Moscicki, R. Lawrence Moss, Trudy V. Murphy, Dennis L. Murray, Angela L. Myers, Simon Nadel, James P. Nataro, Michael N. Neely, William L. Nicholson, Victor Nizet, Amy Jo Nopper, Anna Norrby-Teglund, Theresa J. Ochoa, Miguel O’Ryan, Walter A. Orenstein, Christopher D. Paddock, Diane E. Pappas, Robert F. Pass, Thomas F. Patterson, Stephen I. Pelton, Larry K. Pickering, Caroline Diane Sarah Piggott, Philip A. Pizzo, Andrew J. Pollard, Klara M. Posfay-Barbe, Susan M. Poutanen, Dwight A. Powell, Alice S. Prince, Charles G. Prober, Octavio Ramilo, Shawn J. Rangel, Sarah A. Rawstron, Jennifer S. Read, Michael D. Reed, Joanna J. Regan, Megan E. Reller, Melissa A. Reyes, Peter A. Rice, Samuel E. Rice-Townsend, Frank O. Richards, Gail L. Rodgers, Pierre E. Rollin, José R. Romero, G. Ingrid J.G. Rours, Anne H. Rowley, Sharon L. Roy, Lorry G. Rubin, Guillermo M. Ruiz-Palacios, Lisa Saiman, Laura Sass, Jason B. Sauberan, Peter M. Schantz, Eileen Schneider, Gordon E. Schutze, Benjamin Schwartz, Heidi Schwarzwald, Kara N. Shah, Samir S. Shah, Andi L. Shane, Craig A. Shapiro, Eugene D. Shapiro, Umid M. Sharapov, Jana Shaw, George Kelly Siberry, Jane D. Siegel, Robert David Siegel, Nalini Singh, Upinder Singh, P. Brian Smith, John D. Snyder, David E. Soper, Mary Allen Staat, J. Erin Staples, Jeffrey R. Starke, William J. Steinbach, Ina Stephens, Joseph W. St. Geme, Bradley P. Stoner, Jonathan B. Strober, Kanta Subbarao, Deanna A. Sutton, Douglas Swanson, Leonel T. Takada, Jacqueline E. Tate, Robert V. Tauxe, Marc Tebruegge, Eyasu H. Teshale, George R. Thompson, Herbert A. Thompson, Richard B. Thomson, Emily A. Thorell, Rania A. Tohme, Robert W. Tolan, Philip Toltzis, James Treat, Stephanie B. Troy, Russell B. Van Dyke, Jorge J. Velarde, Jennifer Vodzak, Ellen R. Wald, Geoffrey A. Weinberg, A. Clinton White, Marc-Alain Widdowson, Harold C. Wiesenfeld, John V. Williams, Roxanne E. Williams, Rodney E. Willoughby, Craig M. Wilson, Sarah L. Wingerter, Jerry A. Winkelstein, Kimberly A. Workowski, Terry W. Wright, Pablo Yagupsky, Nada Yazigi, Catherine Yen, Edward J. Young, Andrea L. Zaenglein, and Theoklis E. Zaoutis

Published
2012
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24. Cryptococcus neoformans

Author

Jane M. Gould and Stephen C. Aronoff

Subjects
0303 health sciences, 03 medical and health sciences, 0302 clinical medicine, 030306 microbiology, 030212 general & internal medicine
Published
2011
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27. Histoplasmosis (Histoplasma capsulatum)

Author

Jane M. Gould and Stephen C. Aronoff

Subjects
biology, business.industry, Medicine, business, biology.organism_classification, medicine.disease, Histoplasma capsulatum, Histoplasmosis, Microbiology
Published
2011
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28. Contributors

Author

Jon S. Abramson, Mark J. Abzug, John J. Aiken, H. Hesham A-kader, Cezmi A. Akdis, Harold Alderman, Ramin Alemzadeh, Evaline A. Alessandrini, Omar Ali, Namasivayam Ambalavanan, Karl E. Anderson, Peter M. Anderson, Kelly K. Anthony, Alia Y. Antoon, Stacy P. Ardoin, Carola A.S. Arndt, Stephen S. Arnon, Stephen C. Aronoff, David M. Asher, Barbara L. Asselin, Joann L. Ater, Dan Atkins, Erika F. Augustine, Marilyn Augustyn, Ellis D. Avner, Parvin H. Azimi, Carlos A. Bacino, Robert N. Baldassano, Christina Bales, William F. Balistreri, Robert S. Baltimore, Manisha Balwani, Shahida Baqar, Christine E. Barron, Dorsey M. Bass, Mark L. Batshaw, Richard E. Behrman, Michael J. Bell, John W. Belmont, Daniel K. Benjamin, Michael J. Bennett, Daniel Bernstein, Jatinder Bhatia, Zulfiqar Ahmed Bhutta, Leslie G. Biesecker, James Birmingham, Samra S. Blanchard, Ronald Blanton, Archie Bleyer, C.D.R. Lynelle M. Boamah, Steven R. Boas, Thomas F. Boat, Walter Bockting, Mark Boguniewicz, Daniel J. Bonthius, Laurence A. Boxer, Amanda M. Brandow, David Branski, David T. Breault, Rebecca H. Buckley, Cynthia Etzler Budek, E. Stephen Buescher, Gale R. Burstein, Amaya Lopez Bustinduy, Mitchell S. Cairo, Bruce M. Camitta, Angela Jean Peck Campbell, Rebecca G. Carey, Waldemar A. Carlo, Robert B. Carrigan, Mary T. Caserta, Ellen Gould Chadwick, Lisa J. Chamberlain, Jennifer I. Chapman, Ira M. Cheifetz, Wassim Chemaitilly, Sharon F. Chen, Yuan-Tsong Chen, Russell W. Chesney, Jennifer A. Chiriboga, Robert D. Christensen, Andrew Chu, Michael J. Chusid, Theodore J. Cieslak, Jeff A. Clark, Thomas G. Cleary, John David Clemens, Joanna S. Cohen, Mitchell B. Cohen, Pinchas Cohen, Michael Cohen-Wolkowiez, Robert A. Colbert, F. Sessions Cole, Joanna C.M. Cole, John L. Colombo, Amber R. Cooper, Ronina A. Covar, Barbara Cromer, James E. Crowe, Natoshia Raishevich Cunningham, Steven J. Czinn, Toni Darville, Robert S. Daum, Richard S. Davidson, H. Dele Davies, Peter S. Dayan, Michael R. DeBaun, Guenet H. Degaffe, David R. DeMaso, Mark R. Denison, Arlene E. Dent, Nirupama K. DeSilva, Robert J. Desnick, Gabrielle deVeber, Esi Morgan DeWitt, Chetan Anil Dhamne, Anil Dhawan, Harry Dietz, Lydia J. Donoghue, Patricia A. Donohoue, Mary K. Donovan, John P. Dormans, Daniel A. Doyle, Jefferson Doyle, Stephen C. Dreskin, Denis S. Drummond, Howard Dubowitz, J. Stephen Dumler, Janet Duncan, Paula M. Duncan, LauraLe Dyner, Michael G. Earing, Elizabeth A. Edgerton, Marie Egan, Jack S. Elder, Sara B. Eleoff, Dianne S. Elfenbein, Stephen C. Eppes, Michele Burns Ewald, Jessica K. Fairley, Susan Feigelman, Marianne E. Felice, Eric I. Felner, Edward Fels, Thomas Ferkol, Jonathan D. Finder, Kristin N. Fiorino, David M. Fleece, Patricia M. Flynn, Joel A. Forman, Michael M. Frank, Melvin H. Freedman, Melissa Frei-Jones, Jared E. Friedman, Sheila Gahagan, Paula Gardiner, Luigi Garibaldi, Gregory M. Gauthier, Abraham Gedalia, Matthew J. Gelmini, Michael A. Gerber, K. Michael Gibson, Mark Gibson, Francis Gigliotti, Walter S. Gilliam, Janet R. Gilsdorf, Charles M. Ginsburg, Frances P. Glascoe, Donald A. Goldmann, Denise M. Goodman, Marc H. Gorelick, Gary J. Gosselin, Jane M. Gould, Olivier Goulet, Dan M. Granoff, Michael Green, Thomas P. Green, Larry A. Greenbaum, Marie Michelle Grino, Andrew B. Grossman, David C. Grossman, Alfredo Guarino, Lisa R. Hackney, Gabriel G. Haddad, Joseph Haddad, Joseph F. Hagan, Scott B. Halstead, Margaret R. Hammerschlag, Aaron Hamvas, James C. Harris, Mary E. Hartman, David B. Haslam, Fern R. Hauck, Gregory F. Hayden, Jacqueline T. Hecht, Sabrina M. Heidemann, J. Owen Hendley, Fred M. Henretig, Gloria P. Heresi, Andrew D. Hershey, Cynthia E. Herzog, Jessica Hochberg, Lauren D. Holinger, Jeffrey D. Hord, B. David Horn, William A. Horton, Harish S. Hosalkar, Hidekazu Hosono, Peter J. Hotez, Michelle S. Howenstine, Heather G. Huddleston, Vicki Huff, Denise Hug, Winston W. Huh, Carl E. Hunt, Anna Klaudia Hunter, Patricia Ibeziako, Richard F. Jacobs, Peter Jensen, Hal B. Jenson, Chandy C. John, Michael V. Johnston, Richard B. Johnston, Bridgette L. Jones, James F. Jones, Marsha Joselow, Anupama Kalaskar, Linda Kaljee, Deepak Kamat, Alvina R. Kansra, Sheldon L. Kaplan, Emily R. Katz, James W. Kazura, Virginia Keane, Gregory L. Kearns, Desmond P. Kelly, Judith Kelsen, Kathi J. Kemper, Melissa Kennedy, Eitan Kerem, Joseph E. Kerschner, Seema Khan, Young-Jee Kim, Charles H. King, Stephen L. Kinsman, Adam Kirton, Priya S. Kishnani, Nora T. Kizer, Martin B. Kleiman, Bruce L. Klein, Bruce S. Klein, Michael D. Klein, Robert M. Kliegman, William C. Koch, Patrick M. Kochanek, Eric Kodish, Stephan A. Kohlhoff, Elliot J. Krane, Peter J. Krause, Richard E. Kreipe, Steven E. Krug, John F. Kuttesch, Jennifer M. Kwon, Catherine S. Lachenauer, Stephan Ladisch, Stephen LaFranchi, Oren Lakser, Marc B. Lande, Philip J. Landrigan, Gregory L. Landry, Wendy G. Lane, Philip S. LaRussa, Brendan Lee, Chul Lee, K. Jane Lee, J. Steven Leeder, Rebecca K. Lehman, Michael J. Lentze, Norma B. Lerner, Steven Lestrud, Donald Y.M. Leung, Chris A. Liacouras, Susanne Liewer, Andrew H. Liu, Stanley F. Lo, Franco Locatelli, Sarah S. Long, Anna Lena Lopez, Steven V. Lossef, Jennifer A. Lowry, Kerith Lucco, G. Reid Lyon, Prashant V. Mahajan, Akhil Maheshwari, Joseph A. Majzoub, Asim Maqbool, Ashley M. Maranich, Mona Marin, Joan C. Marini, Morri Markowitz, Kevin P. Marks, Stacene R. Maroushek, Wilbert H. Mason, Christopher Mastropietro, Kimberlee M. Matalon, Reuben K. Matalon, Robert Mazor, Susanna A. McColley, Margaret M. McGovern, Heather S. McLean, Rima McLeod, Peter C. Melby, Joseph John Melvin, Diane F. Merritt, Ethan A. Mezoff, Marian G. Michaels, Alexander G. Miethke, Mohamad A. Mikati, Henry Milgrom, E. Kathryn Miller, Jonathan W. Mink, Grant A. Mitchell, Robert R. Montgomery, Joseph G. Morelli, Anna-Barbara Moscicki, Hugo W. Moser, Kathryn D. Moyer, James R. Murphy, Timothy F. Murphy, Thomas S. Murray, Mindo J. Natale, William A. Neal, Jayne Ness, Kathleen A. Neville, Mary A. Nevin, Jane W. Newburger, Peter E. Newburger, Linda S. Nield, Zehava Noah, Lawrence M. Nogee, Robert L. Norris, Stephen K. Obaro, Makram Obeid, Theresa J. Ochoa, Katherine A. O'Donnell, Robin K. Ohls, Jean-Marie Okwo-Bele, Keith T. Oldham, Scott E. Olitsky, John Olsson, Susan R. Orenstein, Walter A. Orenstein, Judith A. Owens, Charles H. Packman, Michael J. Painter, Priya Pais, Cynthia G. Pan, Vijay Pannikar, Diane E. Pappas, Anjali Parish, John S. Parks, Laura A. Parks, Maria Jevitz Patterson, Pallavi P. Patwari, Timothy R. Peters, Larry K. Pickering, Misha L. Pless, Laura S. Plummer, Craig C. Porter, Dwight A. Powell, David T. Price, Charles G. Prober, Linda Quan, Elisabeth H. Quint, C. Egla Rabinovich, Leslie J. Raffini, Denia Ramirez-Montealegre, Giuseppe Raviola, Ann M. Reed, Harold L. Rekate, Megan E. Reller, Gary Remafedi, Jorge D. Reyes, Geoffrey Rezvani, Iraj Rezvani, A. Kim Ritchey, Frederick P. Rivara, Angela Byun Robinson, Luise E. Rogg, Genie E. Roosevelt, David R. Rosenberg, Melissa Beth Rosenberg, David S. Rosenblatt, Cindy Ganis Roskind, Mary M. Rotar, Ranna A. Rozenfeld, Sarah Zieber Rush, Colleen A. Ryan, H.P.S. Sachdev, Ramesh C. Sachdeva, Mustafa Sahin, Robert A. Salata, Denise A. Salerno, Edsel Maurice T. Salvana, Hugh A. Sampson, Thomas J. Sandora, Tracy Sandritter, Wudbhav N. Sankar, Ajit Ashok Sarnaik, Ashok P. Sarnaik, Harvey B. Sarnat, Minnie M. Sarwal, Mary Saunders, Laura E. Schanberg, Mark R. Schleiss, Nina F. Schor, Bill J. Schroeder, Robert L. Schum, Gordon E. Schutze, Daryl A. Scott, J. Paul Scott, Theodore C. Sectish, George B. Segel, Kriti Sehgal, Ernest G. Seidman, Janet R. Serwint, Dheeraj Shah, Raanan Shamir, Bruce K. Shapiro, Richard J. Shaw, Bennett A. Shaywitz, Sally E. Shaywitz, Meera Shekar, Elena Shephard, Philip M. Sherman, Benjamin L. Shneider, Scott H. Sicherer, Richard Sills, Mark D. Simms, Eric A.F. Simões, Thomas L. Slovis, P. Brian Smith, Mary Beth F. Son, Laura Stout Sosinsky, Joseph D. Spahn, Mark A. Sperling, Robert Spicer, David A. Spiegel, Helen Spoudeas, Jürgen Spranger, Rajasree Sreedharan, Raman Sreedharan, Shawn J. Stafford, Margaret M. Stager, Sergio Stagno, Virginia A. Stallings, Lawrence R. Stanberry, Charles A. Stanley, Bonita F. Stanton, Jeffrey R. Starke, Merrill Stass-Isern, Barbara W. Stechenberg, Leonard D. Stein, William J. Steinbach, Nicolas Stettler, Barbara J. Stoll, Gregory A. Storch, Ronald G. Strauss, Frederick J. Suchy, Karen Summar, Moira Szilagyi, Norman Tinanoff, James K. Todd, Lucy S. Tompkins, Richard L. Tower, Riccardo Troncone, Amanda A. Trott, David G. Tubergen, David A. Turner, Ronald B. Turner, Christina Ullrich, George F. Van Hare, Jakko van Ingen, Heather A. Van Mater, Dick van Soolingen, Scott K. Van Why, Pankhuree Vandana, Douglas Vanderbilt, Jon A. Vanderhoof, Andrea Velardi, Elliott Vichinsky, Linda A. Waggoner-Fountain, Steven G. Waguespack, David M. Walker, Heather J. Walter, Stephanie Ware, Kimberly Danieli Watts, Ian M. Waxman, Debra E. Weese-Mayer, Kathryn Weise, Martin E. Weisse, Lawrence Wells, Jessica Wen, Steven L. Werlin, Michael R. Wessels, Ralph F. Wetmore, Randall C. Wetzel, Isaiah D. Wexler, Perrin C. White, John V. Williams, Rodney E. Willoughby, Samantha L. Wilson, Glenna B. Winnie, Paul H. Wise, Laila Woc-Colburn, Joanne Wolfe, Cynthia J. Wong, Laura L. Worth, Joseph L. Wright, Peter F. Wright, Terry W. Wright, Eveline Y. Wu, Anthony Wynshaw-Boris, Nada Yazigi, Ram Yogev, Marc Yudkoff, Peter E. Zage, Anita K.M. Zaidi, Lonnie K. Zeltzer, Maija H. Zile, Peter Zimmer, and Barry Zuckerman

Published
2011
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30. Contributing Authors

Author

Charalampos Antachopoulos, Louis M. Bell, Jeffrey M. Bergelson, Kristina Bryant, Christine C. Chiou, Jaclyn H. Chu, Susan E. Coffin, Terence S. Dermody, M. Cecilia Di Pentima, Jane C. Edmond, Kathryn M. Edwards, Stephen C. Eppes, Brian T. Fisher, Andrew L. Garrett, Jeffrey S. Gerber, Marc H. Gorelick, Jane M. Gould, Andreas H. Groll, Eric J. Haas, Natasha B. Halasa, Brian D. Hanna, Marvin B. Harper, Fred M. Henretig, David A. Hunstad, Robert N. Husson, Jason Y. Kim, Jean O. Kim, David W. Kimberlin, Joel D. Klein, Grace E. Lee, Doyle J. Lim, Karin L. McGowan, Keith J. Mann, Jason G. Newland, Sheila M. Nolan, Paul A. Offit, Stanley A. Plotkin, Roy Proujansky, Adam J. Ratner, Amy E. Renwick, Carlos D. Rose, Richard M. Rutstein, Ken Schroeter, Michael Sebert, Samir S. Shah, Michael J. Smith, Alan R. Spitzer, Joseph W. St. Geme, Keith H. St. John, Andrew P. Steenhoff, Kathleen E. Sullivan, Philip Toltzis, Jay H. Tureen, Thomas J. Walsh, and Lisa B. Zaoutis

Published
2008
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31. Contributors

Author

Elisabeth E. Adderson, Felice C. Adler-Shohet, Manuel R. Amieva, Gregory L. Armstrong, Wences Arvelo, Ann M. Arvin, David M. Asher, Shai Ashkenazi, Kevin A. Ault, Carol J. Baker, William J. Barson, Beth P. Bell, Michael J. Bell, Daniel K. Benjamin, Stephanie R. Bialek, Margaret J. Blythe, Joseph A. Bocchini, Michael Boeckh, William A. Bower, Kenneth M. Boyer, Christopher R. Braden, John S. Bradley, Michael T. Brady, Denise Bratcher, Paula K. Braverman, Joseph S. Bresee, Itzhak Brook, Kevin E. Brown, John C. Browning, Steven C. Buckingham, E. Stephen Buescher, Jane L. Burns, Michael Cappello, Bryan D. Carter, Ellen Gould Chadwick, Patricia Joan Chesney, James E. Childs, John C. Christenson, Thomas G. Cleary, Susan E. Coffin, Beverly L. Connelly, C. Michael Cotton, Elaine Cox, Robert Andrew Cramer, Maryanne E. Crockett, James E. Crowe, Dennis J. Cunningham, Toni Darville, Gregory A. Dasch, Robert S. Daum, Maite de la Morena, Gail J. Demmler, Dickson D. Despommier, Karen A. Diefenbach, Elidia Dominguez, Stephen M. Downs, Christopher C. Dvorak, Kathryn Edwards, Morven S. Edwards, Janet A. Englund, Véronique Erard, Marina E. Eremeeva, Lyn Finelli, Adam Finn, Anthony E. Fiore, Marc Fischer, Sarah J. Fitch, Patricia M. Flynn, J. Dennis Fortenberry, LeAnne M. Fox, David O. Freedman, Hayley A. Gans, Michael A. Gerber, Francis Gigliotti, Peter Gilligan, Benjamin D. Gold, David L. Goldman, Brahm Goldstein, Susan T. Goldstein, Jane M. Gould, Michael Green, Sharon K. Greene, Mark J. Greenwald, Alexei A. Grom, Leigh B. Grossman, Marta A. Guerra, Kathleen Gutierrez, Judith A. Guzman-Cottrill, Caroline Breese Hall, Marvin B. Harper, David B. Haslam, Edward B. Hayes, J. Owen Hendley, Kelly J. Henrickson, Marion C.W. Henry, Joseph A. Hilinski, Peter J. Hotez, David L. Ingram, Mary Anne Jackson, Richard F. Jacobs, M. Gary Karlowicz, Ben Z. Katz, Jay S. Keystone, David W. Kimberlin, Martin B. Kleiman, Jerome O. Klein, Mark W. Kline, Andrew Y. Koh, Katalin I. Koranyi, E. Kent Korgenski, Robert J. Leggiadro, Moise L. Levy, David B. Lewis, Jay M. Lieberman, Abhijit Limaye, Jacob A. Lohr, Bennett Lorber, Sarah S. Long, Donald E. Low, Gina Lowell, Elizabeth Lowenthal, Jorge Lujan-Zilbermann, Katherine Luzuriaga, Noni E. MacDonald, Yvonne A. Maldonado, Chitra S. Mani, John F. Marcinak, Mario J. Marcon, Gary S. Marshall, Stacey W. Martin, Robert F. Massung, Eric E. Mast, Tony Mazzulli, George H. McCracken, Robert S. McGregor, Kenneth McIntosh, Catherine A. McLean, Rima McLeod, Julia A. McMillan, Jennifer H. McQuiston, H. Cody Meissner, Manoj P. Menon, Marian G. Michaels, Melissa B. Miller, Juan Carlos Millon, John F. Modlin, Matthew R. Moore, Zack S. Moore, Mary M. Moran, Pedro L. Moro, R. Lawrence Moss, Dennis L. Murray, Simon Nadel, James P. Nataro, Michael N. Neely, Victor Nizet, Anna Norrby-Teglund, Ann-Christine Nyquist, Theresa J. Ochoa, Sara M. O'Hara, Walter A. Orenstein, Eduardo Ortega-Barria, Gary D. Overturf, Christopher D. Paddock, John A. Painter, Diane E. Pappas, Monica E. Parise, Robert F. Pass, Thomas F. Patterson, Andrew T. Pavia, Stephen I. Pelton, Georges Peter, Timothy R. Peters, William A. Petri, Larry K. Pickering, Philip A. Pizzo, Andrew J. Pollard, Susan M. Poutanen, Dwight A. Powell, Alice S. Prince, Charles G. Prober, Shawn J. Rangel, Sarah Anne Rawstron, Michael D. Reed, Megan E. Reller, Frank O. Richards, Gail L. Rodgers, Luz I. Romero, Harley A. Rotbart, Anne H. Rowley, Lorry G. Rubin, Guillermo M. Ruiz-Palacios, Xavier Sáez-Llorens, Lisa Saiman, Jason B. Sauberan, Mark H. Sawyer, Peter M. Schantz, Theresa A. Schlager, Gordon E. Schutze, Benjamin Schwartz, Richard H. Schwartz, Heidi Schwarzwald, Samir S. Shah, Andi L. Shane, Eugene D. Shapiro, Avinash K. Shetty, Jane D. Siegel, Robert D. Siegel, Walter E.B. Sipe, Jacek Skarbinski, P. Brian Smith, John D. Snyder, Shahram Solaymani-Mohammadi, Mary Allen Staat, Jeffrey R. Starke, William J. Steinbach, Ina Stephens, Joseph W. St. Geme, Kanta Subbarao, John L. Sullivan, Deanna A. Sutton, Madeline Y. Sutton, David L. Swerdlow, Robert V. Tauxe, Herbert A. Thompson, Richard B. Thomson, Emily A. Thorell, James K. Todd, Philip Toltzis, Theodore F. Tsai, Ellen R. Wald, Richard J. Wallace, Geoffrey A. Weinberg, Avery H. Weiss, A. Clinton White, Marc-Alain Widdowson, Ian T. Williams, John V. Williams, Rodney E. Willoughby, Craig M. Wilson, Jerry A. Winkelstein, Kimberly Workowski, Terry W. Wright, Nada Yazigi, Ram Yogev, Edward J. Young, and Theoklis E. Zaoutis

Published
2008
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32. Capsule enhances pneumococcal colonization by limiting mucus-mediated clearance

Author

Jane M. Gould, Adam J. Ratner, Jeffrey N. Weiser, Kannie Chim, Aoife M. Roche, and Aaron L. Nelson

Subjects
Bacterial capsule, Agglutination, Mucociliary clearance, Phagocytosis, Immunology, Fluorescent Antibody Technique, Microbiology, Pneumococcal Infections, chemistry.chemical_compound, Mice, medicine, Animals, Bacterial Capsules, Mucous Membrane, biology, Mucous membrane, Mucus, Molecular Pathogenesis, Sialic acid, Antibody opsonization, Mice, Inbred C57BL, Infectious Diseases, medicine.anatomical_structure, Streptococcus pneumoniae, chemistry, Mucociliary Clearance, biology.protein, Parasitology, Female, Neuraminidase
Abstract

Expression of a polysaccharide capsule is required for the full pathogenicity of many mucosal pathogens such asStreptococcus pneumoniae. Although capsule allows for evasion of opsonization and subsequent phagocytosis during invasive infection, its role during mucosal colonization, the organism's commensal state, remains unknown. Using a mouse model, we demonstrate that unencapsulated mutants remain capable of nasal colonization but at a reduced density and duration compared to those of their encapsulated parent strains. This deficit in colonization was not due to increased susceptibility to opsonophagocytic clearance involving complement, antibody, or the influx of Ly-6G-positive cells, including neutrophils seen during carriage. Rather, unencapsulated mutants remain agglutinated within lumenal mucus and, thus, are less likely to transit to the epithelial surface where stable colonization occurs. Studies of in vitro binding to immobilized human airway mucus confirmed the inhibitory effect of encapsulation. Likewise, pneumococcal variants expressing larger amounts of negatively charged capsule per cell were less likely to adhere to surfaces coated with human mucus and more likely to evade initial clearance in vivo. Removal of negatively charged sialic acid residues by pretreatment of mucus with neuraminidase diminished the antiadhesive effect of encapsulation. This suggests that the inhibitory effect of encapsulation on mucus binding may be mediated by electrostatic repulsion and offers an explanation for the predominance of anionic polysaccharides among the diverse array of unique capsule types. In conclusion, our findings demonstrate that capsule confers an advantage to mucosal pathogens distinct from its role in inhibition of opsonophagocytosis—escape from entrapment in lumenal mucus.

Published
2006

33. Phase variable desialylation of host proteins that bind to Streptococcus pneumoniae in vivo and protect the airway

Author

Samantha J, King, Karen R, Hippe, Jane M, Gould, Deborah, Bae, Scott, Peterson, Robin T, Cline, Claudine, Fasching, Edward N, Janoff, and Jeffrey N, Weiser

Subjects
Neuraminidase, Pneumonia, Pneumococcal, N-Acetylneuraminic Acid, Immunoglobulin A, Rats, Secretory Component, Lactoferrin, Blood, Streptococcus pneumoniae, Bacterial Proteins, Nasopharynx, Animals, Humans, Oligonucleotide Array Sequence Analysis
Abstract

Most clinical isolates of Streptococcus pneumoniae consist of heterogeneous populations of at least two colony phenotypes, opaque and transparent, selected for in the bloodstream and nasopharynx, respectively. Microarray analysis revealed 24 orfs that demonstrated differences in expression greater than twofold between variants of independent strains. Twenty-one of these showed increased expression in the transparent variants, including 11 predicted to be involved in sugar metabolism. A single genomic region contains seven of these loci including the gene that encodes the neuraminidase, NanA. In contrast to previous studies, there was no contribution of NanA to adherence of S. pneumoniae to epithelial cells or colonization in an animal model. However, we observed NanA-dependent desialylation of human airway components that bind to the organism and may mediate bacterial clearance. Targets of desialylation included human lactoferrin, secretory component, and IgA2 that were shown to be present on the surface of the pneumococcus in vivo during pneumococcal pneumonia. The efficiency of desialylation was increased in the transparent variants and enhanced for host proteins binding to the surface of S. pneumoniae. Because deglycosylation affects the function of many host proteins, NanA may contribute to a protease-independent mechanism to modify bound targets and facilitate enhanced survival of the bacterium.

Published
2004

35. Expression of C-Reactive Protein in the Human Respiratory Tract

Author

Jeffrey N. Weiser and Jane M. Gould

Subjects
Adult, Lipopolysaccharide, Phosphorylcholine, Immunology, Antimicrobial peptides, Respiratory System, Respiratory Mucosa, CHOP, Microbiology, Classical complement pathway, chemistry.chemical_compound, Tumor Cells, Cultured, Humans, Bronchitis, Opsonin, Host Response and Inflammation, Innate immune system, biology, Sputum, Haemophilus influenzae, Immunity, Innate, Anti-Bacterial Agents, Infectious Diseases, C-Reactive Protein, chemistry, biology.protein, Pharynx, Parasitology, Tumor necrosis factor alpha, Protein A
Abstract

C-reactive protein (CRP) is a constituent of normal human serum (NHS) (33). The concentration of CRP in serum is generally less than 2 μg/ml but increases by as much as 1,000-fold in response to a stimulus such as tissue injury or inflammation (5). Following removal of the inflammatory stimulus, CRP levels decline rapidly. These features have made CRP useful as a clinical marker of an inflammatory process, although the function of this acute-phase reactant and its precise role in host defense remain poorly understood. Until recently there had been no demonstration of a direct antimicrobial effect of CRP in vitro, and the study of CRP using animal models has been limited by the marked differences in the regulation of CRP expression in animals compared to humans (27, 46). There is, however, evidence to suggest that CRP contributes to innate immunity. Mice, which have a constitutively low level of CRP expression, are more resistant to experimental pneumococcal sepsis when carrying the human CRP transgene conferring inducible high-level expression as in humans (34). The protective effect of CRP is thought to be mediated by its ability to act as an opsonin and, when bound, to activate the complement by the classical pathway through interaction with complement component C1q (16, 37). The CRP transgene reduces bacteremia following an intraperitoneal inoculation of pneumococci in both decomplemented and complement-expressing mice, suggesting that there is also a complement-independent pathway for CRP-mediated protection, perhaps through direct opsonization (35). CRP received its name because it binds to the C polysaccharide or cell wall teichoic acid of Streptococcus pneumoniae. It is now known that CRP binds in a calcium-dependent manner to choline phosphate or phosphorylcholine (ChoP) residues found on C polysaccharide (38). ChoP had been considered to be a highly unusual structural feature in prokaryotes. It is now clear that in addition to S. pneumoniae, many of the bacterial species that normally inhabit the respiratory tract express ChoP, the molecular target of CRP, on their cell surface. These species are now known to include Streptococcus oralis and S. mitis, Haemophilus influenzae and H. somnus, Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, various Actinomyces species, the commensal Neisseria species, and Mycoplasma species such as M. fermentans (8, 14, 24, 29, 30, 41, 45). The presence of ChoP on a large and diverse collection of species found primarily on the mucosal surface of the airway including gram-positive and gram-negative bacteria, as well as Mollicutes, and its absence from species residing outside the respiratory tract, suggests that this structure contributes to survival in this host environment. Data from both animal models of nasopharyngeal carriage and natural lower respiratory tract infection of humans suggest that ChoP, while not a requirement for survival within the respiratory tract, contributes to the ability of bacteria to persist at these sites (44, 45). The expression of ChoP has been shown to confer resistance to antimicrobial peptides found on the mucosal surface of the upper respiratory tract, such as LL-37, that target structural differences in membranes between host and microbial cells (21). In this regard, the expression of ChoP may allow bacteria to mimic the same structure found on all eukaryotic membrane lipids in the form of phosphatidylcholine. ChoP also allows for bacterial invasion of epithelial cells through interaction with the receptor for platelet-activating factor (rPAF), whose natural ligand, PAF, also contains ChoP (8, 32). CRP, therefore, may contribute to innate immunity by specifically targeting this virulence determinant common to many of the bacterial pathogens of the respiratory tract. A direct antimicrobial effect of CRP, however, has been demonstrated only in the case of H. influenzae, where concentrations of the protein as low as 10 ng/ml bind to ChoP and mediate a complement-dependent bactericidal effect (44). Another striking feature of the ChoP ligand is that there is phase variation in the amount or presence on the bacterial cell surface in many of the species expressing this moiety (17, 40, 42, 45). For H. influenzae, only those phase variants expressing ChoP on their lipopolysaccharide are sensitive to the bactericidal effects of human serum CRP (44). This suggests that these pathogens have developed an efficient means for evasion of clearance mechanisms such as that involving CRP that specifically targets ChoP. The interplay between the expression of ChoP and local amounts of CRP, therefore, may function to maintain the commensal state and limit the pathogenicity of many important respiratory tract bacteria. Human serum CRP is a cyclic pentameric protein of five identical nonglycosylated subunits of 206 amino acids, each with a molecular mass of 24 kDa, that are noncovalently bound to form the mature CRP molecule (13). Serum CRP is synthesized by hepatocytes in the liver as a single-chain precursor with a cleavable signal sequence at the N terminus (36). CRP was initially thought to be produced and secreted only by hepatocytes under induction primarily by interleukin-6 (IL-6), with a synergistic effect of IL- 1 (39, 48). Tumor necrosis factor alpha, transforming growth factor β, and IL-11 have also been shown to affect hepatic CRP expression (3, 4, 10, 15, 23). There is also evidence of CRP expression by Kupffer cells and peripheral blood mononuclear cells, where it was shown to be a membrane protein that is not secreted (12, 19). Although the source and regulation of serum CRP have been extensively studied, the expression of CRP in the human respiratory tract, particularly the heavily colonized upper respiratory tract where organisms bearing its ChoP target reside, has not been addressed. In this report, we show that CRP is found in secretions from the human airway and that epithelial cells lining the mucosal surface of the upper respiratory tract may be a source of this protein. Furthermore, we demonstrate that CRP isolated from the mucosal surface of the airway has antimicrobial activity.

Published
2001

36. Bacterial Phosphorylcholine Decreases Susceptibility to the Antimicrobial Peptide LL-37/hCAP18 Expressed in the Upper Respiratory Tract

Author

Jeffrey N. Weiser, Robert Bals, James M. Wilson, Jane M. Gould, and Elena S. Lysenko

Subjects
Lipopolysaccharide, Membrane lipids, Phosphorylcholine, Immunology, Antimicrobial peptides, Peptide, Biology, CHOP, medicine.disease_cause, Microbiology, Haemophilus influenzae, chemistry.chemical_compound, Cathelicidins, hemic and lymphatic diseases, Nasopharynx, medicine, Humans, Antibacterial agent, chemistry.chemical_classification, Anti-Bacterial Agents, Infectious Diseases, chemistry, Molecular and Cellular Pathogenesis, Parasitology, Carrier Proteins, Antimicrobial Cationic Peptides
Abstract

A number of pathogens of the upper respiratory tract express an unusual prokaryotic structure, phosphorylcholine (ChoP), on their cell surface. We tested the hypothesis that ChoP, also found on host membrane lipids in the form of phosphatidylcholine, acts so as to decrease killing by antimicrobial peptides that target differences between bacterial and host membranes. In Haemophilus influenzae , ChoP is a phase-variable structure on the oligosaccharide portion of the lipopolysaccharide (LPS). There was a bactericidal effect of the peptide LL-37/hCAP18 on a nontypeable H. influenzae strain, with an increasing selection for the ChoP + phase as the concentration of the peptide was raised from 0 to 10 μg/ml. Moreover, constitutive ChoP-expressing mutants of unrelated strains showed up to 1,000-fold-greater survival compared to mutants without ChoP. The effect of ChoP on resistance to killing by LL-37/hCAP18 was dependent on the salt concentration and was observed only when bacteria were grown in the presence of environmental choline, a requirement for the expression of ChoP on the LPS. Further studies established that there is transcription of the LL-37/hCAP18 gene on the epithelial surface of the human nasopharynx in situ and inducible transcription in epithelial cells derived from the upper airway. The presence of highly variable amounts of LL-37/hCAP18 in normal nasal secretions (80 μg/ml) was demonstrated with an antibody against this peptide. It was concluded that ChoP alters the bacterial cell surface so as mimic host membrane lipids and decrease killing by LL-37/hCAP18, an antimicrobial peptide that may be expressed on the mucosal surface of the nasopharynx in bactericidal concentrations.

Published
2000

37. 894Evaluating Clinical Credibility of Surveillance Definitions for Healthcare-Associated Pneumonia and Lower Respiratory Infections

Author

Debra Hess, Pamela Rohrbach, David A. Pegues, Genevieve L. Buser, Shelley S. Magill, Jane M. Gould, Jeffrey R. Miller, Isaac See, Sydney Hubbard, Nicole Gualandi, Andrea Kiernan, Judith O'donnell, Julia Chang, Debra A Smeltz, Susan E. Coffin, Mary Jo Bellush, and Patricia Hennessey

Subjects
medicine.medical_specialty, business.industry, Speech recognition, medicine.disease, IDWeek 2014 Abstracts, Pneumonia, Infectious Diseases, Oncology, Healthcare associated, Poster Abstracts, Credibility, medicine, Intensive care medicine, business
Published
2014
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38. Nontypeable Haemophilus influenzae susceptibility: effect of inoculum size and beta-lactamase production

Author

Jane M. Gould, John J. LiPuma, and Gwendolyn J. Heidecker

Subjects
Microbiology (medical), Colony Count, Microbial, General Medicine, Microbial Sensitivity Tests, Biology, Cefpodoxime, medicine.disease_cause, beta-Lactams, Virology, Haemophilus influenzae, Microbiology, Anti-Bacterial Agents, chemistry.chemical_compound, Minimum inhibitory concentration, Infectious Diseases, Cefprozil, chemistry, medicine, Cefixime, Cefuroxime, Loracarbef, medicine.drug, Antibacterial agent
Abstract

The activities of cefixime, cefpodoxime, cefprozil, cefuroxime, loracarbef, and amoxicillin/clavulanate against 72 clinical isolates of nontypeable Haemophilus influenzae were determined by using an agar dilution method. The effects of beta-lactamase production and bacterial inoculum size were investigated. All antimicrobials exhibited a significant inoculum effect, demonstrating the importance of accurately determining inoculum size in the performance of antimicrobial susceptibility testing of H. influenzae.

Published
1996

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