DOCSLIB.ORG

Review Host-Directed Therapies for Infectious Diseases

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Review Host-Directed Therapies for Infectious Diseases Review Host-directed therapies for infectious diseases: current status, recent progress, and future prospects Alimuddin Zumla, Martin Rao, Robert S Wallis, Stefan H E Kaufmann, Roxana Rustomjee, Peter Mwaba, Cris Vilaplana, Dorothy Yeboah-Manu, Jeremiah Chakaya, Giuseppe Ippolito, Esam Azhar, Michael Hoelscher, Markus Maeurer, for the Host-Directed Therapies Network consortium* Despite extensive global eff orts in the fi ght against killer infectious diseases, they still cause one in four deaths Lancet Infect Dis 2016; worldwide and are important causes of long-term functional disability arising from tissue damage. The continuing 16: e47–63 epidemics of tuberculosis, HIV, malaria, and infl uenza, and the emergence of novel zoonotic pathogens represent *List of consortium partners is major clinical management challenges worldwide. Newer approaches to improving treatment outcomes are needed to available from http://www.unza- uclms.org/hdt-net-partners reduce the high morbidity and mortality caused by infectious diseases. Recent insights into pathogen–host interactions, Centre for Clinical pathogenesis, infl ammatory pathways, and the host’s innate and acquired immune responses are leading to Microbiology, Division of identifi cation and development of a wide range of host-directed therapies with diff erent mechanisms of action. Host- Infection and Immunity, directed therapeutic strategies are now becoming viable adjuncts to standard antimicrobial treatment. Host-directed University College London therapies include commonly used drugs for non-communicable diseases with good safety profi les, immunomodulatory (UCL), London, UK (Prof A Zumla FRCP); National agents, biologics (eg monoclonal antibodies), nutritional products, and cellular therapy using the patient’s own Institute for Health Research immune or bone marrow mesenchymal stromal cells. We discuss clinically relevant examples of progress in identifying Biomedical Research Centre, host-directed therapies as adjunct treatment options for bacterial, viral, and parasitic infectious diseases. UCL Hospitals NHS Foundation Trust, London, UK (Prof A Zumla); Division of Introduction mortality, and end-organ damage, and long-term Therapeutic Immunology, Infectious diseases are leading causes of morbidity functional recovery. A range of host-directed therapies Department of Laboratory and mortality worldwide.1 In high-income countries, have been identifi ed with diff erent mechanisms of action Medicine, Karolinska Institutet, mortality from respiratory tract infections remains high (fi gure 1), and they are now regarded as viable adjuncts to Stockholm, Sweden (M Rao PhD, despite access to quality health services and availability of standard antimicrobial treatment. Host-directed Prof M Maeurer PhD); Centre for antibiotic therapy.1 The intermittent emergence of new therapies can improve host cellular responses to Allogeneic Stem Cell zoonotic pathogens and the increasing incidence of pathogens, target disease-causing virulence factors Transplantation, Karolinska treatment-resistant infections draws attention to the (fi gure 2), and activate innate and adaptive immune University Hospital Huddinge, Stockholm, Sweden (M Rao, 2 limits of the current antimicrobial treatment portfolio responses and immunological memory (fi gure 3). Prof M Maeurer); and the urgent need for alternative management strategies. In evolutionary terms, host–pathogen interactions are Key messages dependent on the microbe surviving without causing • Despite the availability of antimicrobial drugs, infectious diseases are leading causes of harm to the host. The host’s innate and adaptive immune morbidity and mortality worldwide. surveillance mechanisms govern whether the infection • The widespread emergence of antimicrobial resistance calls for novel interventions in will be contained or progress to clinical disease with addition to new antimicrobial development. either recovery or death. Several host factors aff ect • A range of host factors are responsible for development of disease, poor treatment antimicrobial treatment outcome and are responsible for response, and increased mortality. These include immune dysregulation from any progression of disease after infection, poor treatment cause and comorbidity with non-communicable diseases such as diabetes, cancer, response, tissue damage, long-term functional disability, smoking, and chronic obstructive pulmonary disease. and increased mortality. These factors include immune • During the past 4 years, a renaissance of scientifi c research strategies targeting host dysregulation from any cause (aberrant or excess factors—rather than pathogen components directly—is leading to development of a host infl ammatory response to infection, stress, wide range of host-directed therapies that target and modify biological pathways to immunosuppressive drugs, poor living conditions, achieve a positive clinical treatment outcome. socioeconomic factors, micronutrient defi ciencies, HIV, • Host-directed therapies can augment host cellular responses to pathogens, target malnutrition, and alcohol or substance misuse) and disease-causing virulence factors, activate innate and adaptive protective immune comorbidity with non-communicable diseases such as responses, or modulate excessive infl ammation, leading to reduced morbidity, diabetes, cancer, smoking, and chronic obstructive mortality, and end-organ damage. 1 pulmonary disease. • Host-directed therapies include commonly used, safe, and cheap drugs for During the past 4 years, a renaissance of scientifi c non-communicable diseases; biologics; nutritional products; and cellular therapy, research strategies targeting host factors, rather than using the patient’s own immune or mesenchymal stromal cells. pathogen components directly, has opened up novel • The broad spectrum effi cacy of host-directed therapies could also be useful for treatment approaches termed host-directed therapies. A treatment of infectious diseases with epidemic potential, which are associated with host-directed therapy is any product that can augment high mortality. host defence mechanisms or modulate excessive • Host-directed therapies have the additional unique benefi t of preventing or reducing infl ammation, or both, leading to improved clinical the development of antibiotic resistance. treatment outcomes as shown by reduced morbidity, www.thelancet.com/infection Vol 16 April 2016 e47 Review Aurum Institute, Johannesburg, South Africa (Prof R S Wallis MD); Max Planck Institute for Infection Biology, Berlin, Germany (Prof S H E Kaufmann PhD); Monoclonal antibodies Vitamins Repurposed drugs South African Medical Research Council, Cape Town, South CH H Africa (R Rustomjee PhD); NH NH H C University of Zambia-UCL H 3 H N NH2 Medical School (UNZA-UCLMS) H CH3 Research and Training Project, H0 CH University Teaching Hospital, Lusaka, Zambia (P Mwaba PhD); Ministry of Health, Lusaka, Amelioration Zambia (P Mwaba); Unitat de Tuberculosi Experimental Host-directed therapies Fundació Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol CIBER Enfermedades Respiratorias, Can Ruti Campus, Edifici Laboratoris de Disease Recerca, Barcelona, Spain (C Vilaplana PhD); Bacteriology Department, Noguchi Memorial Institute for Medical Research, University of Ghana, Cytokines Cellular therapy Recombinant proteins Legon, Ghana (Prof D Yeboah-Manu PhD); Kenya Medical Research Clinical cure Institute, Nairobi, Kenya (J Chakaya PhD); National Institute for Infectious Figure 1: The main types of host-directed therapies Diseases, Lazzaro Spallanzani, Host-directed therapies focus on ameliorating the severity of disease and improving treatment outcomes. Host-directed therapies constitute a range of therapeutic Rome, Italy (Prof G Ippolito MD); agents such as repurposed drugs, small molecules, synthetic nucleic acids, biologics (such as monoclonal antibodies), cytokines, cellular therapy, recombinant Special Infectious Agents Unit, proteins, and micronutrients. King Fahd Medical Research Centre, and Medical Laboratory Technology Department, Examples of host-directed therapies include commonly with WHO-recommended combination antituberculosis Faculty of Applied Medical used and aff ordable drugs for non-communicable antibiotic therapy. This focus still thrives, although there Sciences, King Abdulaziz diseases with good safety profi les, immunomodulatory are about 2 billion people in the world with latent University, Jeddah, Saudi 89 Arabia (E Azhar PhD); Division agents, biologics, nutritional products, and cellular tuberculosis infection who do not develop active disease. of Infectious Diseases and therapy using the patient’s own immune or mesenchymal Furthermore, the substantial decline in tuberculosis in Tropical Medicine, Medical stromals cells (table 1). See appendix for discussion of Europe and North America in the fi rst half of the Centre of the University of potential host factors for targets of host-directed therapy 19th century occurred well before the antibiotic era. In Munich, Munich, Germany (Prof M Hoelscher PhD); and against infectious disease. 2014, an estimated 1·5 million people died of tuberculosis DZIF German Centre for Studies of host-directed therapies also enable new and there were an estimated 450 000 cases of multidrug- Infection Research, Munich, insights into underlying mechanisms of pathogenesis, resistant (MDR) and extensively drug-resistant (XDR) Germany (Prof M Hoelscher) infl ammatory pathways, and the host’s innate and tuberculosis,89 suggesting that host
Load more

Recommended publications
  • Prophylactic Antibiotics and Prevention of Surgical Site Infections
    Prophylactic Antibiotics and Prevention of Surgical Site Infections Peter A. Najjar, MD, Douglas S. Smink, MD, MPH* KEYWORDS Surgical site infection Prophylactic antibiotics Perioperative infection control KEY POINTS Surgical site infections (SSIs) are the most common type of healthcare-associated infection in the United States, affecting more than 500,000 patients annually. Studies suggest that 40% to 60% of these infections may be preventable. Patients diagnosed with SSI face a 2 to 11 times increase in mortality along with prolonged hospital stays, treatment-associated risks, and potential long-term sequelae. Nationwide efforts to improve SSI rates include monitoring compliance with preventive guidelines via the Surgical Care Improvement Program (SCIP) along with reporting of risk-adjusted infection rates via the National Healthcare Safety Network (NHSN) and the American College of Surgeons National Surgical Quality Improvement Program (ACS- NSQIP). Preoperative prophylaxis with appropriately selected procedure-specific antibiotics administered 1 hour before skin incision is a mainstay of SSI prevention; excess prophy- lactic antibiotic use either through poor selection or continuation postoperatively is a major driver of increased multidrug-resistant organism isolates. Adjunctive measures, such as surgical safety checklists, minimally invasive surgical techniques, and maintenance of perioperative homeostasis, can help further reduce the burden of SSI. INTRODUCTION Healthcare-associated infections (HAIs) present a significant source of preventable morbidity and mortality. More than 30% of all HAIs are represented by surgical site infections (SSIs), making them the most common subtype.1,2 Between 1.9% and Conflict of Interest: None. Department of Surgery, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA * Corresponding author.
    [Show full text]
  • Current Issues and Perspectives in Patients with Possible Sepsis at Emergency Departments
    antibiotics Review Current Issues and Perspectives in Patients with Possible Sepsis at Emergency Departments Ioannis Alexandros Charitos 1, Skender Topi 2, Francesca Castellaneta 3 and Donato D’Agostino 4,* 1 Department of Emergency/Urgency, National Poisoning Center, Riuniti University Hospital (OO.RR.) of Foggia, 71122 Foggia, Italy; [email protected] 2 School of Technical Medical Sciences, University A. Xhuvani, Elbasan 3001, Albania; [email protected] 3 School of Medicine, University of Foggia, 71122 Foggia, Italy; [email protected] 4 Department of Emergency and Organ Transplantation (DETO), School of Medicine, University of Bari A. Moro, 70124 Bari, Italy * Correspondence: donato.d’[email protected] or [email protected]; Tel./Fax: +39-0805595076 Received: 8 April 2019; Accepted: 25 April 2019; Published: 7 May 2019 Abstract: In the area of Emergency Room (ER), many patients present criteria compatible with a SIRS, but only some of them have an associated infection. The new definition of sepsis by the European Society of Intensive Care Medicine and the Society of Critical Care Medicine (2016), revolutionizes precedent criteria, overcoming the concept of SIRS and clearly distinguishing the infection with the patient’s physiological response from the symptoms of sepsis. Another fundamental change concerns the recognition method: The use of SOFA (Sequential-Sepsis Related-Organ Failure Assessment Score) as reference score for organ damage assessment. Also, the use of the qSOFA is based on the use of three objective parameters: Altered level of consciousness (GCS <15 or AVPU), systolic blood pressure 100 mmHg, and respiratory rate 22/min. If patients have at least two of these ≤ ≥ altered parameters in association with an infection, then there is the suspicion of sepsis.
    [Show full text]
  • Antimicrobial Treatment Guidelines for Common Infections
    Antimicrobial Treatment Guidelines for Common Infections June 2016 Published by: The NB Provincial Health Authorities Anti-infective Stewardship Committee under the direction of the Drugs and Therapeutics Committee Introduction: These clinical guidelines have been developed or endorsed by the NB Provincial Health Authorities Anti-infective Stewardship Committee and its Working Group, a sub- committee of the New Brunswick Drugs and Therapeutics Committee. Local antibiotic resistance patterns and input from local infectious disease specialists, medical microbiologists, pharmacists and other physician specialists were considered in their development. These guidelines provide general recommendations for appropriate antibiotic use in specific infectious diseases and are not a substitute for clinical judgment. Website Links For Horizon Physicians and Staff: http://skyline/patientcare/antimicrobial For Vitalité Physicians and Staff: http://boulevard/FR/patientcare/antimicrobial To contact us: [email protected] When prescribing antimicrobials: Carefully consider if an antimicrobial is truly warranted in the given clinical situation Consult local antibiograms when selecting empiric therapy Include a documented indication, appropriate dose, route and the planned duration of therapy in all antimicrobial drug orders Obtain microbiological cultures before the administration of antibiotics (when possible) Reassess therapy after 24-72 hours to determine if antibiotic therapy is still warranted or effective for the given organism or
    [Show full text]
  • Antimicrobial Stewardship
    Antimicrobial Stewardship: Arizona Partnerships Working to Improve the Use of Antimicrobials in the Hospital and Community Part 1 “Antibacterials – indeed, anti-infectives as a whole – are unique in that misuse of these agents can have a negative effect on society at large. Misuse of antibacterials has led to the development of bacterial resistance, whereas misuse of a cardiovascular drug harms only the one patient, not causing a societal consequence.” - Glenn Tillotson; Clin Infect Dis. 2010;51:752 “…we hold closely the principles that antibiotics are a gift to us from prior generations and that we have a moral obligation to ensure that this global treasure is available for our children and future generations.” - David Gilbert, et al (and the Infectious Diseases Society of America). Clin Infect Dis. 2010;51:754-5 A Note To Our Readers and Slide Presenters The objectives of the Subcommittee on Antimicrobial Stewardship Programs are directed at education, presentation, and identification of resources for clinicians to create toolkits of strategies that will assist clinicians with understanding, implementing, measuring, and maintaining antimicrobial stewardship programs. The slide compendium was developed by the Subcommittee on Antimicrobial Stewardship Programs (ASP) of the Arizona Healthcare-Associated Infection (HAI) Advisory Committee in 2012-2013. ASP is a multidisciplinary committee representing various healthcare disciplines working to define and provide guidance for establishing and maintaining an antimicrobial stewardship programs within acute care and long-term care institutions and in the community. Their work was guided by the best available evidence at the time although the subject matter encompassed thousands of references. Accordingly, the Subcommittee selectively used examples from the published literature to provide guidance and evidenced-based criteria regarding antimicrobial stewardship.
    [Show full text]
  • Antimicrobials and Resistance | Microbiology and Risk Factors for Transmission | Table of Contents | APIC
    11/2/2017 26. Antimicrobials and Resistance | Microbiology and Risk Factors for Transmission | Table of Contents | APIC Antimicrobials and Resistance Author(s): Forest W. Arnold, DO, MSc, FIDSA Assistant Professor, Division of Infectious Diseases University of Louisville Hospital Epidemiologist University of Louisville Hospital Louisville, KY Published: November 1, 2017 Abstract Although infection prevention traditionally has approached the problem of resistance primarily from the aspect of preventing transmission from an infected patient to a noninfected patient, more needs to be done to improve how antimicrobials are commonly used. Antimicrobial use is the main selective pressure responsible for the increasing resistance seen in hospitals. Patients come to possess a resistant pathogen either by transmitting bacteria that already have the resistance gene in place or by having their bacteria acquire a gene that codes for resistance. The former is more common because it merely requires a handshake while the latter takes days to weeks to develop. To have an impact on antimicrobial use so as to reduce resistance, infection preventionists (IPs) need a working knowledge of available antimicrobials, principles for their appropriate use, the mechanisms by which these drugs inhibit microbial growth, and the mechanisms by which microorganisms develop resistance. In addition, IPs need to understand promising new strategies to improve antimicrobial use and how members of the infection prevention community can become more involved. Key Concepts Although infection prevention traditionally has approached the problem of resistance primarily from the aspect of preventing transmission, more needs to be done to control how antimicrobials are commonly used. Antimicrobial stewardship is the best investment for preventing the proliferation of multidrug-resistant pathogens and the adverse events associated with the drugs used to treat such pathogens.
    [Show full text]
  • IDSA/ATS Consensus Guidelines on The
    SUPPLEMENT ARTICLE Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults Lionel A. Mandell,1,a Richard G. Wunderink,2,a Antonio Anzueto,3,4 John G. Bartlett,7 G. Douglas Campbell,8 Nathan C. Dean,9,10 Scott F. Dowell,11 Thomas M. File, Jr.12,13 Daniel M. Musher,5,6 Michael S. Niederman,14,15 Antonio Torres,16 and Cynthia G. Whitney11 1McMaster University Medical School, Hamilton, Ontario, Canada; 2Northwestern University Feinberg School of Medicine, Chicago, Illinois; 3University of Texas Health Science Center and 4South Texas Veterans Health Care System, San Antonio, and 5Michael E. DeBakey Veterans Affairs Medical Center and 6Baylor College of Medicine, Houston, Texas; 7Johns Hopkins University School of Medicine, Baltimore, Maryland; 8Division of Pulmonary, Critical Care, and Sleep Medicine, University of Mississippi School of Medicine, Jackson; 9Division of Pulmonary and Critical Care Medicine, LDS Hospital, and 10University of Utah, Salt Lake City, Utah; 11Centers for Disease Control and Prevention, Atlanta, Georgia; 12Northeastern Ohio Universities College of Medicine, Rootstown, and 13Summa Health System, Akron, Ohio; 14State University of New York at Stony Brook, Stony Brook, and 15Department of Medicine, Winthrop University Hospital, Mineola, New York; and 16Cap de Servei de Pneumologia i Alle`rgia Respirato`ria, Institut Clı´nic del To`rax, Hospital Clı´nic de Barcelona, Facultat de Medicina, Universitat de Barcelona, Institut d’Investigacions Biome`diques August Pi i Sunyer, CIBER CB06/06/0028, Barcelona, Spain. EXECUTIVE SUMMARY priate starting point for consultation by specialists. Substantial overlap exists among the patients whom Improving the care of adult patients with community- these guidelines address and those discussed in the re- acquired pneumonia (CAP) has been the focus of many cently published guidelines for health care–associated different organizations, and several have developed pneumonia (HCAP).
    [Show full text]
  • Clinical Microbiology
    Clinical Microbiology Antibiotics are medicines used to fight bacterial infections. There are different types of antibiotics. Each type is only effective against certain bacteria. An antibiotic sensitivity test can help find out which antibiotic will be most effective in treating your infection. The test can also be helpful in finding a treatment for antibiotic-resistant infections. Antibiotic resistance happens when standard antibiotics become less effective or ineffective against certain bacteria. Antibiotic resistance can turn once easily treatable diseases into serious, even life- threatening illnesses. Antibiotic sensitivity testing or Antibiotic susceptibility testing is the measurement of the susceptibility of bacteria to antibiotics. It is used because bacteria may have resistance to some antibiotics. Sensitivity testing results can allow a clinician to change the choice of antibiotics from empiric therapy, which is when an antibiotic is selected based on clinical suspicion about the site of an infection and common causative bacteria, to directed therapy, in which the choice of antibiotic is based on knowledge of the organism and its sensitivities. Sensitivity testing usually occurs in a medical laboratory, and may be based on culture methods that expose bacteria to antibiotics, or genetic methods that test to see if bacteria have genes that confer resistance. Culture methods often involve measuring the diameter of areas without bacterial growth, called zones of inhibition, around paper discs containing antibiotics on agar culture dishes that have been evenly inoculated with bacteria. The minimum inhibitory concentration, which is the lowest concentration of the antibiotic that stops the growth of bacteria, can be estimated from the size of the zone of inhibition.
    [Show full text]
  • ADULT SEPSIS SCREEN and TREATMENT ALGORITHM BAYLOR UNIVERSITY MEDICAL CENTER Publication Year: 2013
    ADULT SEPSIS SCREEN AND TREATMENT ALGORITHM BAYLOR UNIVERSITY MEDICAL CENTER Publication Year: 2013 Summary: Hospital: Baylor University Medical Center The development and implementation of a nursing driven sepsis screening protocol and Location: Dallas, Texas treatment algorithm. Contact: John S Garrett, Associate Medical Director, Department of Emergency Medicine [email protected] Category: Hospital Metrics: . A: Arrival . Annual ED Volume: 117,571 . Hospital Beds: 1,065 . B: Bed Placement . Ownership: Baylor Healthcare System, . C: Clinician Initial Evaluation & Not-For-Profit Throughput . Trauma Level: 1 . E: Exit from the ED . Teaching Status: Yes Key Words: . Sepsis . Triage Tools Provided: . BHCS Adult Sepsis Screen & Treatment Algorithm Tools Provided: . Hahnemann University Hospital Clinical Areas Affected: Staff Involved: Triage Plan . Emergency Department . ED Staff . Nurses . Pharmacists . Physicians . Technicians Copyright © 2002‐2013 Urgent Matters 1 Innovation Severe sepsis and septic shock are major drivers of in-hospital mortality, with rates that are over 8 times higher than those associated with other inpatient admissions. When coupled with an apparent rise in incidence: hospital admission rates for severe sepsis and septic shock doubled between 2000 and 2008, sepsis is projected to be a growing source of mortality, morbidity, and healthcare cost within the United States. This data is especially pertinent to Emergency Departments (ED): effective treatments for patients with severe sepsis and septic shock are time-sensitive whereby early recognition and treatment significantly impacts mortality. Based upon growing evidence that rapid recognition and aggressive treatment significantly improves outcomes, the Surviving Sepsis Campaign (SSC) recently released updated guidelines detailing a standard operating procedure for early risk stratification and management of patients with severe sepsis and septic shock.
    [Show full text]
  • AS Clinical Teaching Tool
    AS Clinical Teaching Tool Use this tool to debrief on 1. Antibiotic Stewardship. Antibiotic stewardship involves the judicious antimicrobial stewardship use of antibiotics and can be described as guardianship of a limited principles for the patients resource (antibiotics) in order to preserve their activity for the future. you are seeing in the More specifically, it can be described as prescribing the right drug for clinical area. the right patient for the right indication for the right duration at the right dose. At the level of the individual patient, What are some ways that you practice antibiotic stewardship? What are some tools you use to ensure that the antibiotics you recommend or prescribe are given for the right indication, dose, and duration? What factors should be considered when considering whether a case is appropriate for stewardship interventions vs a formal infectious diseases consultation? 2. Empiric vs directed therapy. Empiric therapy is necessary for clinical conditions that require prompt therapy to reduce morbidity and mortality, whereas directed therapy is prescribed when diagnostic information is available. Choose a patient from the consult list who was prescribed an empiric antibiotic regimen. A Discuss instances where empiric therapy is indicated. Discuss 1-2 alternative antibiotic regimens that could be considered. What are the pros and cons of various regimens? Be sure to address potential for collateral damage, adverse effects, etc. Discuss what information is needed in order to change the patient’s antibiotic regimen from empiric to directed therapy. Discuss situations in which empiric antibiotics may be withheld. For example, antibiotics may be B withheld pending information on more targeted therapy in patients with osteomyelitis without cellulitis or systemic illness.
    [Show full text]
  • Pneumonia-Antibiotic-Treatment Executive
    Comparative Effectiveness Review Number 136 Effective Health Care Program Pharmacokinetic/Pharmacodynamic Measures for Guiding Antibiotic Treatment for Hospital- Acquired Pneumonia Executive Summary Background Effective Health Care Program Hospital-Acquired Pneumonia: The Effective Health Care Program Epidemiology was initiated in 2005 to provide valid Hospital-acquired (or nosocomial) evidence about the comparative pneumonia (HAP) is the second most effectiveness of different medical common hospital-acquired infection. interventions. The object is to help It occurs especially in the elderly, consumers, health care providers, and immunocompromised patients, surgical others in making informed choices patients, and individuals receiving enteral among treatment alternatives. Through feeding through a nasogastric tube. The its Comparative Effectiveness Reviews, incidence rates for HAP, which can occur the program supports systematic in all areas of hospitals, range from 5 to appraisals of existing scientific more than 20 per 1,000 admissions.1,2 evidence regarding treatments for high-priority health conditions. It HAP is the leading cause of hospital- also promotes and generates new acquired infection in the intensive care scientific evidence by identifying gaps unit (ICU).1 Almost one-third of HAP in existing scientific evidence and episodes are acquired in ICUs;3 as many supporting new research. The program as 90 percent of ICU cases may be puts special emphasis on translating ventilator associated.3,4 In the ICU setting, findings into a variety of useful HAP accounts for up to 25 percent of all formats for different stakeholders, infections and for more than 50 percent of including consumers. the antibiotics prescribed.1 The full report and this summary are Guidelines issued in 2005 by the available at www.effectivehealthcare.
    [Show full text]
  • Diagnostic and Clinical Aspects of Invasive Fungal Disease After Allogeneic Hematopoietic Stem Cell Transplantation
    DEPARTMENT OF LABORATORY MEDICINE Karolinska Institutet, Stockholm, Sweden DIAGNOSTIC AND CLINICAL ASPECTS OF INVASIVE FUNGAL DISEASE AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION Ola Blennow Stockholm 2014 Cover picture: Thoracic CT showing a dense infiltrate with halo sign (top), and hyphae in a lung biopsy (bottom). All previously published papers were reproduced with permission from the publisher. Published by Karolinska Institutet. Printed by Åtta.45 Tryckeri AB © Ola Blennow, 2014 ISBN 978-91-7549-690-0 Institutionen för laboratoriemedicin Diagnostic and Clinical Aspects of Invasive Fungal Disease after Allogeneic Hematopoietic Stem Cell Transplantation AKADEMISK AVHANDLING som för avläggande av medicine doktorsexamen vid Karolinska Institutet offentligen försvaras i föreläsningssal R64, Karolinska Universitetsjukhuset, Huddinge Fredagen den 17 oktober 2014, kl 09.00 av Ola Blennow MD Huvudhandledare: Fakultetsopponent: Docent Jonas Mattsson Professor Kieren Marr Karolinska Institutet Johns Hopkins University School of Medicine Institutionen för onkologi och patologi Department of Infectious Diseases Centrum för allogen stamcellstransplantation (CAST) Betygsnämnd: Docent Stig Lenhoff Bihandledare: Lunds Universitet Professor Per Ljungman Avdelningen för hematologi och Karolinska Institutet transfusionsmedicin Institutionen för medicin, Huddinge Enheten för hematologi Professor Christine Wennerås Göteborgs Universitet Avdelningen för infektionssjukdomar Professor Bertil Christensson Lunds Universitet Stockholm 2014 Avdelningen
    [Show full text]
  • Comparative Effectiveness of Narrow-Spectrum Antibiotics Versus Broad-Spectrum Antibiotics in the Treatment of Community-Acquired Pneumonia in Adults
    Future Research Prioritization: Comparative effectiveness of narrow-spectrum antibiotics versus broad-spectrum antibiotics in the treatment of community-acquired pneumonia in adults Prepared for: Patient-Centered Outcomes Research Institute (PCORI) 1828 L St., NW, Suite 900 Washington, DC 20036 Phone: (202) 827-7700 Fax: (202) 355-9558 www.pcori.org Prepared by: Johns Hopkins Evidence-Based Practice Center Baltimore, Maryland Investigators: Sydney Dy, MD, MSc Susan Hutfless, PhD Catalina Suarez-Cuervo, MD Acknowledgments: John Bartlett, MD and Sara Cosgrove, MD, MS October 2015 1 INTRODUCTION Community-acquired pneumonia (CAP) is defined as an infection of the lung in persons who have not been hospitalized recently or exposed to other health care settings that markedly increase risk of contracting pneumonia. Health care-associated pneumonia is defined and treated differently than CAP. In 2012, 1.1 million persons were diagnosed with CAP in the United States, resulting in 327,840 hospital admissions.1 Characteristics of individuals at increased susceptibility to CAP include older age, comorbidities, immunosuppression, non-white race, and lower education and income. In 2013, CAP was the 9th leading cause of death in the US with a mortality rate of 16.9 per 100,000 contributing to 53,000 deaths.2 The national total cost (both direct and indirect) is estimated at $10.6 billion per year.3,4 Typical symptoms of CAP include fever, cough, sputum production, and shortness of breath, with leukocytosis on laboratory testing and lung consolidation or infiltrate on chest imaging. However, the diagnosis of CAP can be challenging, as some patients, especially those who are elderly or have comorbidities, may not present with these symptoms and signs.
    [Show full text]