Comparative Effectiveness Review Number 78 Procalcitonin-Guided Antibiotic Therapy Comparative Effectiveness Review Number 78 Procalcitonin-Guided Antibiotic Therapy Prepared for: Agency for Healthcare Research and Quality U.S. Department of Health and Human Services 540 Gaither Road Rockville, MD 20850 www.ahrq.gov Contract No. 290-2007-10058-I Prepared by: Blue Cross and Blue Shield Association Technology Evaluation Center Evidence-based Practice Center Chicago, IL Investigators: Nilam J. Soni, M.D. David J. Samson, M.S. Jodi L. Galaydick, M.D. Vikrant Vats, Ph.D. David L. Pitrak, M.D. Naomi Aronson, Ph.D. AHRQ Publication No. 12(13)-EHC124-EF October 2012 This report is based on research conducted by the Blue Cross and Blue Shield Association Technology Evaluation Center Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290-2007- 10058-I). The findings and conclusions in this document are those of the authors, who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ. Therefore, no statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services. The information in this report is intended to help health care decisionmakers—patients and clinicians, health system leaders, and policymakers, among others—make well-informed decisions and thereby improve the quality of health care services. This report is not intended to be a substitute for the application of clinical judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information, i.e., in the context of available resources and circumstances presented by individual patients. This report may be used, in whole or in part, as the basis for development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied. This document is in the public domain and may be used and reprinted without special permission except those copyrighted materials that are clearly noted in the document. Further reproduction of those copyrighted materials is prohibited without the specific permission of copyright holders. Persons using assistive technology may not be able to fully access information in this report. For assistance contact [email protected]. None of the investigators have any affiliations or financial involvement that conflicts with the material presented in this report. Suggested citation: Soni NJ, Samson DJ, Galaydick JL, Vats V, Pitrak DL, Aronson N. Procalcitonin-Guided Antibiotic Therapy. Comparative Effectiveness Review No. 78. (Prepared by the Blue Cross and Blue Shield Association Technology Evaluation Center Evidence-based Practice Center under Contract No. 290-2007-10058-I.) AHRQ Publication No. 12(13)-EHC124- EF. Rockville, MD: Agency for Healthcare Research and Quality. October 2012. www.effectivehealthcare.ahrq.gov/reports/final.cfm. ii Preface The Agency for Healthcare Research and Quality (AHRQ) conducts the Effective Health Care Program as part of its mission to organize knowledge and make it available to inform decisions about health care. As part of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003, Congress directed AHRQ to conduct and support research on the comparative outcomes, clinical effectiveness, and appropriateness of pharmaceuticals, devices, and health care services to meet the needs of Medicare, Medicaid, and the Children’s Health Insurance Program (CHIP). AHRQ has an established network of Evidence-based Practice Centers (EPCs) that produce Evidence Reports/Technology Assessments to assist public- and private-sector organizations in their efforts to improve the quality of health care. The EPCs now lend their expertise to the Effective Health Care Program by conducting comparative effectiveness reviews (CERs) of medications, devices, and other relevant interventions, including strategies for how these items and services can best be organized, managed, and delivered. Systematic reviews are the building blocks underlying evidence-based practice; they focus attention on the strength and limits of evidence from research studies about the effectiveness and safety of a clinical intervention. In the context of developing recommendations for practice, systematic reviews are useful because they define the strengths and limits of the evidence, clarifying whether assertions about the value of the intervention are based on strong evidence from clinical studies. For more information about systematic reviews, see www.effectivehealthcare.ahrq.gov/reference/purpose.cfm. AHRQ expects that CERs will be helpful to health plans, providers, purchasers, government programs, and the health care system as a whole. In addition, AHRQ is committed to presenting information in different formats so that consumers who make decisions about their own and their family’s health can benefit from the evidence. Transparency and stakeholder input are essential to the Effective Health Care Program. Please visit the Web site (www.effectivehealthcare.ahrq.gov) to see draft research questions and reports or to join an email list to learn about new program products and opportunities for input. Comparative effectiveness reviews will be updated regularly. We welcome comments on this CER. They may be sent by mail to the Task Order Officer named below at: Agency for Healthcare Research and Quality, 540 Gaither Road, Rockville, MD 20850, or by email to [email protected]. Carolyn M. Clancy, M.D. Jean Slutsky, P.A., M.S.P.H. Director Director, Center for Outcomes and Evidence Agency for Healthcare Research and Quality Agency for Healthcare Research and Quality Stephanie Chang, M.D., M.P.H. Supriya Janakiraman, M.D., M.P.H. Director, EPC Program Task Order Officer Center for Outcomes and Evidence Center for Outcomes and Evidence Agency for Healthcare Research and Quality Agency for Healthcare Research and Quality iii Acknowledgments The authors gratefully acknowledge the following individuals for their contributions to this project: Claudia Bonnell, R.N., M.L.S.; Lisa Garofalo; Mark Grant, M.D., M.P.H.; Steven Gutman, M.D.; Lisa Sarsany, M.A.; Kathleen Ziegler, Pharm.D.; Elbert Huang, M.D., M.P.H; Ronald Thisted, Ph.D.; Michael Douglas, M.S.; and Jessica Hoag, B.A. Technical Expert Panel R. Phillip Dellinger, M.D. Joshua Metlay, M.D., Ph.D. Head, Critical Care Medicine Professor of Medicine, Epidemiology, and Cooper University Hospital Emergency Medicine Camden, NJ Perelman School of Medicine University of Pennsylvania Jesse Hall, M.D. Philadelphia, PA Section Chief, Pulmonary and Critical Care Medicine Emanuel Rivers, M.D., M.P.H. University of Chicago Vice Chair and Director of Research for the Chicago, IL Department of Emergency Medicine Henry Ford Hospital Stephen Kahn, Ph.D. Detroit, MI Associate Director, Clinical Laboratories Loyola University Chicago Gregory Schmidt, M.D. Maywood, IL Director, Critical Care Programs University of Iowa Henry Masur, M.D. Iowa City, IA Chief, Critical Care Medicine National Institutes of Health Bethesda, MD Peer Reviewers Derek Angus, M.D., M.P.H. Rongwei (Rochelle) Fu, Ph.D. Professor and Chair, Critical Care Medicine Associate Professor Professor, Medicine and Health Policy Oregon Health & Science University and Management Portland, OR University of Pittsburgh School of Medicine Pittsburgh, PA iv Procalcitonin-Guided Antibiotic Therapy Structured Abstract Objectives. To systematically review comparative studies of the use of procalcitonin in the clinical management of adult and pediatric patients with suspected local or systemic infection. Data sources. MEDLINE®, Embase®, the Cochrane Database of Systematic Reviews, National Institute for Clinical Excellence, the National Guideline Clearinghouse, and the Health Technology Assessment Programme were searched from January 1, 1990, to December 16, 2011; the MEDLINE, Embase, and Cochrane searches were updated in December 2011. A search of the gray literature included databases with regulatory information, clinical trial registries, abstracts and conference papers, grants and federally funded research, and information from manufacturers. Review methods. We sought studies that compared procalcitonin-guided versus clinical-criteria- guided initiation, discontinuation, or change of antibiotic therapy. Outcomes were antibiotic use, mortality, morbidity, and adverse drug events of antibiotic therapy. Data were abstracted by a single reviewer and fact-checked by a second reviewer. Study quality was assessed using the U.S. Preventive Services Task Force framework. A meta-analysis on short-term mortality in intensive care unit (ICU) patients was performed using a random-effects model. Strength of the body of evidence was assessed according to the AHRQ Methods Guide. Results. There were 18 randomized, controlled trials that addressed five patient populations. Procalcitonin guidance reduces antibiotic use when used to discontinue antibiotics in adult ICU patients and to initiate or discontinue antibiotics in patients with respiratory tract infections (high evidence), without increasing morbidity (moderate evidence) and mortality (low evidence). In contrast, procalcitonin-guided