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2 OKU ® Orthopaedic Knowledge Update ® Musculoskeletal Infection

M. Daniel Wongworawat, MD, FAAOS EDITOR

Orthopaedic Knowledge Update ® 2 OKU ® Musculoskeletal Infection

Copyright © Wolters Kluwer, Inc. Unauthorized reproduction of the content is prohibited. 2023

Copyright © Wolters Kluwer, Inc. Unauthorized reproduction of the content is prohibited. 2023

Orthopaedic Knowledge Update ® 2 OKU ® Musculoskeletal Infection

EDITOR M. Daniel Wongworawat, MD, FAAOS Professor, Department of Orthopaedic Surgery Loma Linda University Health Loma Linda, California

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Board of Directors, 2023-2024 Kevin J. Bozic, MD, MBA, FAAOS President Paul Tornetta III, MD, PhD, FAAOS First Vice President Annunziato Amendola, MD, FAAOS Second Vice President Michael L. Parks, MD, FAAOS Treasurer Felix H. Savoie III, MD, FAAOS Past President Alfonso Mejia, MD, MPH, FAAOS Chair, Board of Councilors Joel L. Mayerson, MD, FAAOS Chair-Elect, Board of Councilors Michael J. Leddy III, MD, FAAOS Secretary, Board of Councilors Armando F. Vidal, MD, FAAOS Chair, Board of Specialty Societies Adolph J. Yates Jr, MD, FAAOS Chair-Elect, Board of Specialty Societies Michael P. Bolognesi, MD, FAAOS Secretary, Board of Specialty Societies Lisa N. Masters Lay Member Evalina L. Burger, MD, FAAOS Member at Large Chad A. Krueger, MD, FAAOS Member at Large Toni M. McLaurin, MD, FAAOS Member at Large Monica M. Payares, MD, FAAOS Member at Large Thomas E. Arend Jr, Esq, CAE Chief Executive Officer (ex-officio)

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The material presented in the Orthopaedic Knowledge Update ® : Musculoskeletal Infection 2 has been made available by the American Academy of Orthopaedic Surgeons (AAOS) for educational purposes only. This material is not intended to present the only, or necessarily best, methods or procedures for the medical situations discussed, but rather is intended to represent an approach, view, state ment, or opinion of the author(s) or producer(s), which may be helpful to others who face similar situations. Medical providers should use their own, independ ent medical judgment, in addition to open discussion with patients, when devel oping patient care recommendations and treatment plans. Medical care should always be based on a medical provider’s expertise that is individually tailored to a patient’s circumstances, preferences and rights. Some drugs or medical devices demonstrated in AAOS courses or described in AAOS print or electronic publica tions have not been cleared by the Food and Drug Administration (FDA) or have been cleared for specific uses only. The FDA has stated that it is the responsibility of the physician to determine the FDA clearance status of each drug or device he or she wishes to use in clinical practice and to use the products with appro priate patient consent and in compliance with applicable law. Furthermore, any statements about commercial products are solely the opinion(s) of the author(s) and do not represent an Academy endorsement or evaluation of these products. These statements may not be used in advertising or for any commercial purpose. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form, or by any means, electronic, mechanical, photocopying, recording, or otherwise, without prior written per mission from the publisher. AAOS does not grant permission for AAOS-owned content to be ingested into any AI chatbot, unless approved. ISBN 978-1-9752-0242-2 Library of Congress Control Number: Cataloging in Publication data available on request from publisher. Printed in Mexico Published 2025 by the American Academy of Orthopaedic Surgeons

Staff American Academy of Orthopaedic Surgeons Anna Salt Troise, MBA, Chief Commercial Office Hans Koelsch, PhD, Director, Publishing Lisa Claxton Moore, Senior Manager, Editorial Steven Kellert, Senior Editor 9400 West Higgins Road Rosemont, Illinois 60018 Copyright 2025 by the American Academy of Orthopaedic Surgeons Copyright © Wolters Kluwer, Inc. Unauthorized reproduction of the content is prohibited. 2023

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Acknowledgments

Editorial Board, Orthopaedic Knowledge Update ® : Musculoskeletal Infection 2 Editor M. Daniel Wongworawat, MD, FAAOS Professor, Department of Orthopaedic Surgery Loma Linda University Health Loma Linda, California

Sandra B. Nelson, MD Associate Clinical Director Division of Infectious Diseases Massachusetts General Hospital Assistant Professor

Harvard Medical School Boston, Massachusetts Aaron J. Tande, MD, FIDSA Associate Professor of Medicine Consultant, Division of Public Health, Infectious Diseases, and Occupational Medicine Chair, Orthopedic Infectious Diseases Focus Group Rochester, Minnesota Charalampos G. Zalavras, MD, PhD, FAAOS, FACS Professor, Department of Orthopaedic Surgery University of Southern California Los Angeles, California

Section Editors Barry D. Brause, MD, FACP, FIDSA Chief Emeritus Division of Infectious Diseases Department of Medicine Hospital for Special Surgery Attending Physician

New York Presbyterian Hospital Professor of Clinical Medicine Weill Medical College of Cornell University New York, New York Elie S. Ghanem, MD, FAAOS Associate Professor Department of Orthopedic Surgery University of Missouri at Columbia Columbia, Missouri Brian A. Klatt, MD, FAAOS Associate Professor Chief, Division of Adult Reconstruction Department of Orthopaedic Surgery

University of Pittsburgh Pittsburgh, Pennsylvania

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Contributors

Serkan Akçay, MD Attending, Orthopaedic Surgery and Traumatology Department of Orthopaedic Surgery Reyap Hospitals Istanbul, Turkey Keenan D. Atwood, MD Department of Orthopaedics West Virginia University School of Medicine Morgantown, West Virginia Maja Babic, MD Assistant Professor Department of Infectious Diseases Cleveland Clinic Lerner College of Medicine Cleveland Clinic Cleveland, Ohio Larry M. Baddour, MD, FIDSA, FAHA Professor Emeritus Division of Public Health, Infectious Diseases, and Occupational Medicine Departments of Medicine and Cardiovascular Medicine Mayo Clinic College of Medicine and Science Rochester, Minnesota Catalina Baez, MD Postdoctoral Research Fellow Department of Orthopaedic Surgery

Antonia F. Chen, MD, MBA, FAAOS Associate Professor Department of Orthopaedic Surgery Harvard University Brigham and Women’s Hospital

Boston, Massachusetts Niall Cochrane, MD Department of Orthopaedics Duke University Durham, North Carolina Lawson A. Copley, MD, MBA, FAAOS Professor of Orthopaedic Surgery and Pediatrics University of Texas Southwestern Dallas, Texas P. Maxwell Courtney, MD, FAAOS Associate Professor Department of Orthopaedic Surgery Rothman Orthopaedics at Thomas Jefferson University Philadelphia, Pennsylvania Carl Deirmengian, MD, FAAOS Professor, Rothman Orthopaedic Institute

Thomas Jefferson University Philadelphia, Pennsylvania Matthew J. Dietz, MD, FAAOS Chair and Associate Professor Department of Orthopaedics West Virginia University School of Medicine Morgantown, West Virginia Bülent M. Ertu ğ rul, MD Professor of Infectious Diseases and Clinical Microbiology Department of Infectious Diseases

University of Florida Gainesville, Florida Olivier Borens, MD Professor, Bone and Motion Center Clinic Bois-Cerf, Hirslanden

Lausanne, Switzerland Victor R. Carlson, MD Hip and Knee Fellow OrthoCarolina

Reyap Hospitals Istanbul, Turkey Yale A. Fillingham, MD, FAAOS Assistant Professor Rothman Orthopaedic Institute

Charlotte, North Carolina Laura Certain, MD, PhD Clinical Associate Professor Department of Medicine Thomas Jefferson University Philadelphia, Pennsylvania Copyright © Wolters Kluwer, Inc. Unauthorized reproduction of the content is prohibited. 2023

University of Utah Salt Lake City, Utah

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Contributors

Jonathon M. Florance, MD Department of Orthopaedics Duke University Durham, North Carolina Elie S. Ghanem, MD, FAAOS Associate Professor

Joya-Rita Hindy, MD Research Collaborator Division of Public Health, Infectious Diseases, and Occupational Medicine Department of Medicine Mayo Clinic College of Medicine and Science Rochester, Minnesota Paul D. Holtom, MD Adjunct Professor Department of Medicine and Orthopaedics Keck School of Medicine University of Southern California Los Angeles, California Cole Howie, MD Department of Internal Medicine University of Iowa Iowa City, Iowa Jason E. Hsu, MD, FAAOS Associate Professor Department of Orthopaedics and Sports Medicine University of Washington Medical Center Seattle, Washington Patrick Kelly, MD Department of Orthopaedic Surgery Duke University Durham, North Carolina Patrick J. Kellam, MD Assistant Professor Department of Orthopaedics McGovern Medical School at The University of Texas Health Science Center at Houston Houston, Texas Jihye Kim, PharmD

Department of Orthopedic Surgery University of Missouri at Columbia Columbia, Missouri Jeremy M. Gililland, MD, FAAOS Associate Professor Department of Orthopaedic Surgery University of Utah Salt Lake City, Utah Graham S. Goh, MD Department of Orthopaedic Surgery Boston University

Boston, Massachusetts Sara F. Haddad, MD Research Collaborator Division of Public Health, Infectious Diseases, and Occupational Medicine Department of Medicine Mayo Clinic College of Medicine and Science Rochester, Minnesota Mark A. Haimes, MD, MS Assistant Professor Department of Orthopedic Surgery and Rehabilitation

University of Vermont Burlington, Vermont Michael W. Henry, MD Associate Attending Physican Department of Medicine Hospital for Special Surgery

New York, New York Noreen J. Hickok, PhD Professor, Department of Orthopaedic Surgery Clinical Assistant Professor Department of Pharmacy Virginia Commonwealth University Richmond, Virginia Randall Marcus, MD, FAAOS Professor, Department of Orthopaedic Surgery Case Western Reserve University School of Medicine Cleveland, Ohio Copyright © Wolters Kluwer, Inc. Unauthorized reproduction of the content is prohibited. 2023 Thomas Jefferson University Philadelphia, Pennsylvania Carlos A. Higuera, MD Chairman, Levitetz Department of Orthopaedic Surgery Cleveland Clinic Florida Weston, Florida

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Contributors

Willem-Jan Metsemakers, MD, PhD Professor, Department of Trauma Surgery University Hospitals Leuven Leuven, Belgium Andy O. Miller, MD Associate Attending Physican Department of Medicine Hospital for Special Surgery

Jakrapun Pupaibool, MD, MS Clinical Associate Professor Department of Medicine

University of Utah Salt Lake City, Utah Noah J. Quinlan, MD Department of Orthopaedic Surgery and Sports Medicine Bassett Healthcare

New York, New York Sandra B. Nelson, MD Associate Clinical Director Division of Infectious Diseases Assistant Professor Harvard Medical School Massachusetts General Hospital Boston, Massachusetts William T. Obremskey, MD, MPH, MMHC, FAAOS Professor, Department of Orthopaedic Surgery Vanderbilt University Medical Center Nashville, Tennessee Michael J. O’Malley, MD, FAAOS Assistant Professor, University of Pittsburgh Director of Education, UPMC Adult Reconstruction Fellowship Department of Orthopaedic Surgery, UPMC Pittsburgh, Pennsylvania Tejbir S. Pannu, MD, MS Orthopaedic Surgery Research Fellow Levitetz Department of Orthopaedic Surgery Cleveland Clinic Florida Weston, Florida

Cooperstown, New York James P. Reynolds, MD Spine Fellow OrthoCarolina Charlotte, North Carolina Julie E. Reznicek, DO Associate Professor Division of Infectious Diseases Virginia Commonwealth University Richmond, Virginia William J. Rubenstein, MD Orthopaedic Surgeon Orthopaedic Arthroplasty Attending

Sports Medicine North Peabody, Massachusetts Jessica L. Seidelman, MD, MPH Assistant Professor Department of Medicine Duke University Durham, North Carolina Parham Sendi, MD Professor, Department of Infectious Diseases Institute for Infectious Diseases University of Bern Bern, Switzerland Thorsten M. Seyler, MD, PhD, FAAOS Associate Professor Department of Orthopaedics Duke University Durham, North Carolina Claus S. Simpfendorfer, MD Assistant Professor Department of Diagnostic Radiology Cleveland Clinic Lerner College of Medicine

Javad Parvizi, MD, FAAOS, FRCS Professor of Orthopaedic Surgery Department of Orthopaedic Surgery Rothman Orthopaedic Institute Philadelphia, Pennsylvania Michael J. Patzakis, MD, FAAOS Professor Emeritus

Department of Orthopaedic Surgery University of Southern California Los Angeles, California Luis Pulido, MD Orthopaedic Surgeon North Central Florida Division of Florida Orthopaedic Institute Gainesville, Florida Cleveland Clinic Cleveland, Ohio Copyright © Wolters Kluwer, Inc. Unauthorized reproduction of the content is prohibited. 2023

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Contributors

John Sontich, MD, FAAOS Associate Professor Department of Orthopaedic Surgery Case Western Reserve University School of Medicine Cleveland, Ohio Alex Soriano, MD Department of Infectious Diseases Clinic Hospital Barcelona, Spain Taylor Stauffer, BS Medical Student Duke University School of Medicine Durham, North Carolina Milan Stevanovic, MD, PhD, FAAM Professor, Department of Orthopaedics Keck School of Medicine of USC Los Angeles, California Paul Stoodley, PhD, FAAM Professor, Departments of Microbial Infection and Immunity The Ohio State University Columbus, Ohio Don Bambino Geno Tai, MD, MBA Assistant Professor Division of Infectious Diseases and International Medicine

Isaac P. Thomsen, MD, MSCI Associate Professor Pediatric Infectious Diseases

Vanderbilt University Medical Center Monroe Carell, Jr. Children’s Hospital at Vanderbilt Nashville, Tennessee

Ilker Uçkay, MD Titular Professor

Head of Infectious Diseases, Head of Clinical Research Service of Infectious Diseases and Infection Control Department of Orthopedic Surgery Balgrist University Hospital University of Zurich Zurich, Switzerland Kenneth L. Urish, MD, PhD, FAAOS, FAOA Associate Professor Department of Orthopaedic Surgery and Bioengineering Loma Linda University Loma Linda, California Marjan Wouthuyzen-Bakker, MD, PhD Internist-Infectiologist Department of Medical Microbiology and Infection Prevention University Medical Center Groningen University of Groningen Groningen, The Netherlands Charalampos G. Zalavras, MD, PhD, FAAOS, FACS Professor, Department of Orthopaedic Surgery University of Southern California Los Angeles, California University of Pittsburgh Pittsburgh, Pennsylvania M. Daniel Wongworawat, MD, FAAOS Professor, Department of Orthopaedic Surgery

University of Minnesota Minneapolis, Minnesota Saad Tarabichi, MD Postdoctoral Research Fellow Department of Orthopaedic Surgery Rothman Orthopaedic Institute Philadelphia, Pennsylvania Alexander M. Tatara, MD, PhD Clinical Staff Division of Infectious Diseases Massachusetts General Hospital Boston, Massachusetts

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Preface

and irrigation solutions and techniques. With recent advances in antibiotic therapy, an entire section is devoted to this topic. An in-depth review of anti biotic therapy is presented, covering general principles, local and systemic delivery, and specific considerations for different types of bone and joint infections. It also discusses the role of long-term antibiotic suppression in some cases. The second half of the book addresses clinical scenarios of musculoskeletal infection—prosthetic joint infections, fracture-related infections, and other bone and joint and soft-tissue infections, including pediatric infections, hand and foot infections, spine infections, and necrotizing fasciitis. Chapters discuss the latest advances in diagnosis, surgical treatment, and antibiotic therapy for these conditions. The editors and authors hope that this book will be a useful resource for residents, fellows, and practitioners who aim to provide optimal professional care to patients with musculoskeletal infection.

Orthopaedic Knowledge Update ® : Musculoskeletal Infection 2 is a comprehensive and updated guide to the diagnosis, prevention, and management of muscu loskeletal infection, a complex and challenging prob lem that affects millions of people around the world. Musculoskeletal infection can cause severe complications for patients, their families, and the healthcare system, and it requires a multidisciplinary approach involv ing surgeons, infectious disease specialists, and basic scientists. This book aims to provide a comprehensive and up-to-date overview of the current knowledge and best practices in the diagnosis, prevention, and treatment of musculoskeletal infection. Because the first edition of this book was published by AAOS in 2009, all chapters in this second edition have been newly written to reflect the recent advances in the field. The first section discusses general aspects of muscu loskeletal infection, such as epidemiology, risk factors, and risk reduction strategies. It also explores the basic science of infection, including diagnostic biomarkers and methods, microbiology of pathogens, biofilm biology,

M. Daniel Wongworawat, MD, FAAOS Editor

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Contents

Chapter 6 Patient Optimization for Infection Prevention . . . . . . . . . . . . 47 Catalina Baez, MD Luis Pulido, MD

Section 1: General Considerations SECTION EDITOR Elie S. Ghanem, MD, FAAOS

Section 2: Basic Science

Chapter 1 The Epidemiology of Musculoskeletal Infections . . . . . . . . . . . . . 3 Cole Howie, MD Elie S. Ghanem, MD, FAAOS Chapter 2 Local Patient Risk Factors . . . . . . 11 Matthew J. Dietz, MD, FAAOS Keenan D. Atwood, MD Chapter 3 Systemic Patient Risk Factors . . . . 21 Tejbir S. Pannu, MD, MS Carlos A. Higuera, MD Chapter 4 Operating Room Environmental RiskFactors . . . . . . . . . . . .31 Graham S. Goh, MD Yale A. Fillingham, MD, FAAOS Chapter 5 Perioperative Strategies to Reduce Surgical Site Infection . . . . . . . .41 Jeremy M. Gililland, MD, FAAOS Carl Deirmengian, MD, FAAOS Yale A. Fillingham, MD, FAAOS P. Maxwell Courtney, MD, FAAOS Chapter 8 Microbiology of Musculoskeletal Infections . . . . . . . . . . . . .69 Michael W. Henry, MD Andy O. Miller, MD Chapter 9 Biofilm . . . . . . . . . . . . . .81 Noreen J. Hickok, PhD Kenneth L. Urish, MD, PhD, FAAOS, FAOA Paul Stoodley, PhD, FAAM Chapter 10 Irrigants and Irrigation . . . . . . . 91 Antonia F. Chen, MD, MBA, FAAOS William J. Rubenstein, MD Copyright © Wolters Kluwer, Inc. Unauthorized reproduction of the content is prohibited. 2023 Victor R. Carlson, MD Patrick J. Kellam, MD James P. Reynolds, MD SECTION EDITOR Barry D. Brause, MD, FACP, FIDSA Chapter 7 General Diagnostics . . . . . . . . 61

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Chapter 16 Surgical Treatment of Hip and Knee Prosthetic Joint Infections . . .165 Mark A. Haimes, MD, MS Michael J. O’Malley, MD, FAAOS Chapter 17 Surgical Management of Prosthetic Joint Infection of the Shoulder . . . 181 Noah J. Quinlan, MD Jason E. Hsu, MD, FAAOS Chapter 18 Antibiotic Treatment of Prosthetic Joint Infections . . . . . . . . . .195 Laura Certain, MD, PhD Jakrapun Pupaibool, MD, MS Section 5: Fracture-Related Infections SECTION EDITOR Charalampos G. Zalavras, MD, PhD, FAAOS, FACS

Section 3: Antibiotics

SECTION EDITOR Sandra B. Nelson, MD

Chapter 11 Antibiotics: General Principles of Use in Orthopaedic Infections . . . 105 Julie E. Reznicek, DO Jihye Kim, PharmD Chapter 12 Local Antibiotic Delivery Methods.............115 Niall Cochrane, MD Taylor Stauffer, BS Jonathon M. Florance, MD Patrick Kelly, MD Thorsten M. Seyler, MD, PhD, FAAOS Chapter 13 Systemic Antibiotic Therapy . . . . 129 Jessica L. Seidelman, MD, MPH Marjan Wouthuyzen-Bakker, MD, PhD Alex Soriano, MD Chapter 14 Long-Term Antibiotic Suppression . .143 Alexander M. Tatara, MD, PhD Sandra B. Nelson, MD

Section 4: Prosthetic Joint Infections Chapter 19 Definition, Diagnosis, and Socioeconomic Effect of Fracture-Related Infections . . . . 209 Willem-Jan Metsemakers, MD, PhD William T. Obremskey, MD, MPH, MMHC, FAAOS Chapter 20 Prevention of Infection in Open Fractures . . . . . . . . . . . .221 Michael J. Patzakis, MD, FAAOS Charalampos G. Zalavras, MD, PhD, FAAOS, FACS Chapter 21 Management of Fracture-Related Infections . . . . . . . . . . . . 229 Charalampos G. Zalavras, MD, PhD, FAAOS, FACS Paul D. Holtom, MD John Sontich, MD, FAAOS Randall Marcus, MD, FAAOS Copyright © Wolters Kluwer, Inc. Unauthorized reproduction of the content is prohibited. 2023 SECTION EDITOR Brian A. Klatt, MD, FAAOS Chapter 15 Diagnosis of Prosthetic Joint Infection. . . . . . . . . . . . .155 Saad Tarabichi, MD Javad Parvizi, MD, FAAOS, FRCS

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Contents

Chapter 25 Hand Infections . . . . . . . . . 273 M. Daniel Wongworawat, MD, FAAOS Milan Stevanovic, MD, PhD Chapter 26 Infections of the Spine . . . . . . .281 Maja Babic, MD Claus S. Simpfendorfer, MD Chapter 27 Necrotizing Fasciitis and Other Complicated Skin and Soft-Tissue Infections . . . . . . . . . . . . 293 Joya-Rita Hindy, MD Sara F. Haddad, MD Larry M. Baddour, MD, FIDSA, FAHA Index . . . . . . . . . . . . . . 307

Section 6: Bone, Joint, and Soft-Tissue Infections

SECTION EDITOR Aaron J. Tande, MD, FIDSA

Chapter 22 Pediatric Musculoskeletal Infections 243 Isaac P. Thomsen, MD, MSCI Lawson A. Copley, MD, MBA, FAAOS Chapter 23 Septic Arthritis in Adults . . . . . 253 Don Bambino Geno Tai, MD, MBA Olivier Borens, MD Parham Sendi, MD Chapter 24 Diabetic Foot Infections . . . . . . 263 Bülent M. Ertuğrul, MD Serkan Akçay, MD İlker Uçkay, MD

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CHAPTER

Surgical Treatment of Hip and Knee Prosthetic Joint Infections

MARK A. HAIMES, MD, MS • MICHAEL J. O’MALLEY, MD, FAAOS

ABSTRACT Prosthetic joint infection (PJI) is a devastating condition with high morbidity and mortality. With the increased number of hip and knee replacements being performed, the expected number of PJIs is likely to increase as well. Treatment is usually surgical; however, the choice of surgical procedure is not universally agreed on. The spec trum of surgical treatment includes débridement with exchange of modular components (débridement, antibiot ics, and implant retention), revision of all components in either a single-stage or two-stage manner, or a salvage procedure. A two-stage revision of components is the standard treatment for chronic PJI in the United States; however, single-stage revision is becoming more common internationally and in some centers in the United States. Débridement, antibiotics, and implant retention is commonly used for the treatment of acute infections with less virulent organisms and when patients cannot tolerate a full revision of components. The 1.5-stage procedure has resulted, as some patients and surgeons have both decided to defer second-stage reimplantation because of their satisfaction with their temporary spacer. The surgical options should be weighed to consider the patient’s symptoms, microbiology, medical comorbidities, prior surgeries/implants, and goals for quality of life. When all other options are most likely to fail, salvage procedures should be discussed with the patient.

Section 4: Prosthetic Joint Infections

Keywords: 1.5-stage revision; antibiotics, débride ment, and implant retention; prosthetic joint infection; single-stage revision; two-stage revision

arthroplasty with reimplantation at one or two stages, arthrodesis, resection arthroplasty alone, or amputation. There is no universal standard treatment and there are differences in practice based on the region of the world. However, there are general guidelines and strong evi dence in certain cases that can help surgeons plan the appropriate surgical treatment of PJI of the hip or knee.

INTRODUCTION Generally, the treatment of prosthetic joint infection (PJI) consists of both surgical débridement and antimicrobial therapy. The proper surgical and antimicrobial approach depends on the timing of symptoms, microbiology, sta bility of prosthesis, quality of soft-tissue envelope, and individual patient function. Surgical options include débridement with retention of prosthesis, resection

DÉBRIDEMENT, ANTIBIOTICS, AND IMPLANT RETENTION Indications A 2019 literature review discussed the traditional indi cations for a débridement, antibiotics, and implant retention (DAIR) procedure: patients with a PJI who have well-fixed components, absence of a sinus tract, less than 3 weeks of symptoms, less than 4 weeks since index surgery, or those for whom alternative surgi cal strategies are unacceptable. 1 DAIR has obvious appeal if successful in that the retention of well-fixed Dr. O’Malley or an immediate family member serves as a paid consultant to or is an employee of Smith & Nephew and Stryker. Neither Dr. Haimes nor any immediate family member has received anything of value from or has stock or stock options held in a commercial company or institution related directly or indirectly to the subject of this chapter. Copyright © Wolters Kluwer, Inc. Unauthorized reproduction of the content is prohibited. 2023

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Section 4: Prosthetic Joint Infections

components avoids the patient morbidity associated with removing the implants and the subsequent more difficult recovery. Surgical Technique The least-invasive surgical treatment of PJI is the arthroscopic DAIR procedure. A 2020 study reported only a 15% to 20% success rate for arthroscopic DAIR; subsequently, the procedure has become less common because of the low likelihood of success. 2 These results are most likely due to the inability to exchange modu lar components. The exchange of modular components (polyethylene in total knee arthroplasty [TKA] or head and liner in total hip arthroplasty) allows for not only removal of foreign material with a potential biofilm but also better visualization and the ability to perform a more thorough débridement. Therefore, there is no current role for arthroscopic DAIR in hip and knee PJI. 2 Appropriate DAIR procedures consist of an open arthrotomy, extensive débridement of the synovium, irrigation, and removal and exchange of modular compo nents. A 2020 study supported the exchange of modular components when possible. 3 The procedure itself differs among surgeons in the extent of the débridement/syn ovectomy as well as the local delivery of antibiotics and irrigation solutions. The optimal extent of débridement or local adjunct treatment of antibiotics and irrigation is yet to be determined. However, at the second International Consensus Meeting (ICM) on Musculoskeletal Infection, there was strong group consensus recommending irriga tion with 6 to 9 L of fluid. 4 Postoperatively, patients are treated with intravenous antibiotics for 6 weeks, followed by oral antibiotic sup pression for an extended period. A 2020 retrospective review supported giving 3 to 6 months of extended oral antibiotic treatment with one study advocating for 1 year. 5 Outcomes The overall success of a DAIR in the literature varies widely, from zero to 90%. 6,7 The likelihood of suc cess depends the timing of symptoms, microbiology, laboratory study results, the ability to exchange mod ular components, and patient comorbidities. 6-11 With recent protocols, one study from 2019 found that 84% of patients who underwent DAIR for PJI were free of infection at 2 years. 12 Another study has less-promising results, reporting a 4-year failure of 57% and a 5-year mortality of 20%. 13 The timing of symptoms is an important prognos tic indicator. In a retrospective analysis of 99 patients who underwent DAIR for PJI, 88% of patients with less than 2 days of symptoms were successfully treated in contrast to 55% with more than 2 days of symptoms. 7

In a 2019 study of 83 patients who underwent DAIR, the mean time from onset of symptoms to surgery was 6.2 days for successfully treated patients versus 10.7 days for those with treatment failure. 11 This shifts the urgency of the DAIR procedure, once indicated, to days rather than weeks. The infectious organism also plays a significant role in predicting successful treatment with a DAIR proce dure. Staphylococcus aureus PJIs have a higher failure rate when compared with Staphylococcus epidermidis or streptococcal species. 14 This finding has persisted throughout the literature with reports of 71% failure rate of S aureus PJI versus 30% failure rate of S epidermidis PJI. 8 Another study reported a success rate of 74% for streptococcal infections versus 50% for staphylococcal infection. 7 Reported outcomes with methicillin-resis tant S aureus continue to show a high failure rate of DAIR, as high as 84%. 9 Finally, two studies from 2019 reported that polymicrobial, antibiotic-resistant species, and fungal infections also have been shown to have a sig nificantly higher failure rate when performing DAIR. 15,16 Several host factors have been associated with failed DAIR treatment. A 2019 retrospective review of 199 patients who underwent DAIR for PJI found treatment failure associated with multiple factors after multivar iate analysis, including acute hematogenous infection, previous revision surgery, and increased Charlson Comorbidity Index. 15 Diabetes mellitus, chronic obstruc tive pulmonary disease, and history of malignancy were patient comorbidities associated with treatment failure. 15 Predictive algorithms have been developed to guide treat ment decisions. The KLIC-score (kidney, liver, index sur gery, cemented prosthesis, and C-reactive protein value) is shown to be predictive of early failure of DAIR. 17 The CRIME80 score (C-reactive protein greater than 150 mg/L, chronic obstructive pulmonary disease, rheuma toid arthritis, fracture as indication for the prosthesis, male sex, not exchanging the mobile components during débridement, and age older than 80 years [+2, +1, +3, +3, +1, +1, and +2, respectively]) can be useful in predicting treatment failure in late acute infections. A score of 3 or greater was associated with higher treatment failure and mortality with a DAIR procedure when compared with implant removal 10 ( Table 1 ).

Section 4: Prosthetic Joint Infections

There is a concern that undergoing a DAIR procedure causes worse outcomes for a subsequent two-stage revi sion. A multicenter retrospective cohort study demon strated 28 failures (34%) of 83 knees that underwent a two-stage revision TKA after previous DAIR. 18 The authors attribute this high failure rate for two-stage revi sion TKA to the initial DAIR procedure itself. This study has limitations because it lacks a comparative group of patients and no evidence that the DAIR procedure itself caused an increase in subsequent two-stage revision TKA Copyright © Wolters Kluwer, Inc. Unauthorized reproduction of the content is prohibited. 2023

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Chapter 16: Surgical Treatment of Hip and Knee Prosthetic Joint Infections

with PJI and extensive instrumentation who were retro spectively reviewed, 56 underwent DAIR procedure and 31 underwent two-stage revision. 6 There was no differ ence in outcomes for those who underwent DAIR versus two-stage revision in terms of revision surgery or mor tality; however, more patients in the DAIR cohort were ambulatory (76.8% versus 54.8%) and maintained a functional bending knee joint (85.7% versus 45.2%). The decision to undergo DAIR versus a two-stage revision was made by the treating surgeon, introducing potential bias to the groups. However, 27% of the patients who underwent DAIR had symptoms for longer than 4 weeks and 25% had a draining sinus. These previously consid ered contraindications for a DAIR procedure seem to still allow for reasonable results in these difficult situations. It is important to note that antibiotics were continued indefinitely in the DAIR population in this study. DAIR can be a successful treatment option if the indications are appropriate. The timing of surgery is critical and, if possible, patients should undergo surgery within days of diagnosis. Patients with streptococcal or S epidermidis infection have better results than those with S aureus infection, antimicrobial-resistant organism infection, polymicrobial infections, or fungal infections. Extended oral antibiotics after 6 weeks of intravenous antibiotics increase the rate of successful DAIR. DAIR procedure failed in patients with an acute hematogenous infection, bacteremia, elevated erythrocyte sedimentation rate, diabetes, chronic obstructive pulmonary disease, or previous revision surgery. However, in the appropriate setting, patients with extensive hardware may benefit from an attempted DAIR procedure and chronic sup pressive antibiotics rather than the morbidity associated with a two-stage revision. Future studies are needed to find the ideal irrigation solutions that have the highest yield for infection control, what antibiotic regimen and duration is most appropriate, and which local antibiotic delivery modality is best. Genomic sequencing may play a role in the future to improve pathogen identification and tailor appropriate treatment. TWO-STAGE REVISION ARTHROPLASTY The most commonly used treatment for hip and knee PJI in North America is a two-stage revision of components. First described in 1983, the components are removed during the first procedure, along with extensive débride ment and irrigation. 24 Commonly, a temporary spacer is placed to maintain the joint space and deliver antibiotics locally. The patient is placed on parenteral antibiotics for a period of 6 to 12 weeks and a second surgery is per formed with repeat débridement and irrigation followed by reimplantation of new components. Outside of chronic PJI, other indications include conditions in which DAIR

Table 1

CRIME80 Score Used to Predict Treatment Failure Chronic obstructive pulmonary disease

+2 +1 +3 +3 +1 +1

C-reactive protein >150 mg/L

Rheumatoid arthritis

Fracture as indication for the prosthesis

Male sex

Not exchanging the modular components

Age older than 80 years +2 A score of 3 or above is associated with higher treatment failure and mortality with a débridement, antibiotics, and implant retention pro cedure compared with implant removal.

failure. Other studies have questioned these findings and have not shown an increase in failure rate of subsequent two-stage treatment after a failed DAIR procedure. 19-22 A 2019 multicenter retrospective review of 291 patients with knee PJI included 63 patients who underwent two stage revision TKA alone and 228 who underwent DAIR and had a mean follow-up of 6.2 years. 22 Seventy-five patients underwent DAIR, which was unsuccessful, and subsequent two-stage revision TKA. This study demon strated 72% success in the failed DAIR group and 81% in the staged-only group. This difference was not sig nificant, and considering the morbidity of a two-stage revision TKA, and it was concluded that DAIR is a rea sonable treatment attempt. There has been increased interest in attempting DAIR in the more complex cases of PJI. This includes patients who previously underwent a two-stage revision or in the case of extensive instrumentation for which com plete explant of hardware would have very high morbid ity. One study analyzed 60 patients (42 knees, 18 hips) whose two-stage revisions had failed who then under went subsequent procedures. 23 A DAIR procedure was performed in 37 cases, resulting in failure in 21 patients (57%). Forty patients underwent a two-stage revision TKA (17 from the DAIR group). Outcomes also were poor in the two-stage revision group, with only 26 of 40 patients (65%) undergoing second-stage reimplantation and only 16 patients (40%) of those remained infection free at 2-year follow-up. The authors note that DAIR has a high failure rate, but the outcomes of a two-stage revision are also very poor, so there are limited options in this setting. Another group of patients with complex issues includes those with extensive instrumentation and PJI. Extensive instrumentation has been defined as long revision prostheses, fully cemented constructs, and those with ingrown cones or sleeves. In a group of 87 patients

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Section 4: Prosthetic Joint Infections

or a single-stage procedure is more likely to fail such as PJI with active sepsis or virulent/resistant pathogens. Stage One and Antibiotic Spacers The first stage involves the removal of implants, extensive débridement, and usually, the insertion of an antibiotic spacer. Implant removal can be extremely complex and time consuming if the implants are well-fixed. The goal with any implant removal is to perform an extensive synovectomy and preserve as much bone as possible. Techniques to remove implants are beyond the scope of this chapter but are integral to master when performing revisions for infection. Inserting a spacer during the interval between the first and second stage of a two-stage revision serves several purposes. It maintains the joint space and often can be a functional joint, providing patients com fort and making reimplantation easier. In addition, spacers are used to deliver antibiotics locally, which may aid in infection control. Spacers can be defined as static (nonarticulating) or dynamic (articulating). Dynamic spacers can be made entirely of cement or composed of normal arthroplasty components with a metal-on-polyethylene articulation, commonly referred to as a low-friction spacer. Knee A 2019 study reported on the use of static spacers as a temporary arthrodesis with antibiotic-loaded cement between the femur and tibia, usually with an intramedul lary device extending into the diaphysis of the femur and tibia. 25 These serve to maintain the joint space and pro vide increased stability of the knee. These are generally indicated for severe bone loss, collateral ligament insuf ficiency ( Figure 1 ), periarticular fracture, or extensor mechanism disruption. 26,27 Articulating cement spacers can be prefabricated or made intraoperatively. The benefit of the prefabricated spacers ( Figure 2 ) is time saved in the operating room. However, the antibiotic agent present in the prosthesis cannot be tailored to the sensitivities of the pathogen. Limitations of these spacers include patient discomfort, as they often report a grinding sensa tion with joint movement. In addition, these spacers can dislodge or fracture ( Figure 3 ). Low-friction spacers are gaining popularity because the joint feels more normal to patients ( Figure 4 ). Concerns regarding the use of metal and polyethylene in an infected joint are expected, but a 2020 study reported no increase in failure or subsequent reinfection with these spacers. 28 Some surgeons place antibiotic dowels in the medullary canal to help stabi lize the implant and to deliver additional antibiotics. A 2019 study evaluating their use reported no increase in infection eradication. 29

A

B

C

D

Hip Nonarticulating (Girdlestone) spacers in the hip are usually composed of packed antibiotic-laden cement in the acetab ulum and in the open femoral canal ( Figure 5 ). Antibiotic beads can also be used. The primary indication for nonar ticulating hip spacers is inadequate bone stock to support a dynamic spacer. Similar to the knee, dynamic spacers in the hip vary in design and composition. Hip spacers can be prefabricated with antibiotic cement or can be sized and molded intraoperatively. Real-component, low-friction spacers have gained popularity in the hip as well ( Figure 6 ). The benefit of articulating spacers is that the patient obtains a functioning hip during the interval between stages. Complications however have been described, including fracture, bone erosion, and dislocation. A and B , Lateral and AP radiographs showing pre vious hinged total knee arthroplasty with collateral ligament insufficiency. C and D , AP and Lateral radiographs show the same knee with subsequent prosthetic joint infection treated with static spacer rather than an articulating spacer because of collateral ligament insufficiency. FIGURE 1

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Chapter 16: Surgical Treatment of Hip and Knee Prosthetic Joint Infections

than 2 g of vancomycin per 40-g bag of cement in the spacer construct, as a decrease in treatment failure has been reported. 20 Two randomized controlled trials comparing static and articulating spacers, one published in 2020 for knees 30 and the other published in 2021 for hips, 31 demonstrate favorable outcomes with articulating spacers. Sixty-eight patients undergoing two-stage exchange for knee PJI were randomized to either static spacer or articulating spacer made intraoperatively with the use of silicone molds. The static spacer group had a longer hospital stay (6.1 versus 5.1 days), decreased arc of motion at follow-up (100° versus 113°), and lower Knee Society Score (69.8 versus 79.4). Although not statistically signifi cant, there was also a greater need for extensile exposure at the time of reimplantation (16.7% versus 4.0%) and a higher reoperation rate (25.0% versus 8.0%) in the static spacer group. 30 Fifty-two patients undergoing two-stage exchange for hip PJI were randomized to either static spacer or articulating spacer made intraoperatively with the use of silicone molds. There was no difference in sur gical time at second-stage reimplantation (143 minutes static versus 145 articulating). Hospital stay was longer in the static cohort after stage one (8.6 versus 5.4 days) and stage two (6.3 versus 3.6 days). Although it did not reach statistical significance, the static cohort was more often discharged to an extended care facility after stage one (65% versus 30%, P = 0.056). 31 The optimal spacer construct has yet to be determined. In a systematic meta-analysis of 34 articles containing

B

A

FIGURE 2 A and B , Plain lateral and AP radiographs show a total knee arthroplasty prosthetic knee infection treated with a prefabricated cement spacer.

The antibiotics used in the spacer should be tailored to the infectious organism, as well as bactericidal, water soluble, and thermodynamically stable. These include most commonly tobramycin, gentamycin, and vancomy cin. Spacers have varying antibiotic compositions with no randomized controlled trials to compare them. 28 However, there is evidence to support the use of more

Section 4: Prosthetic Joint Infections

A FIGURE 3 A , AP and Lateral radiographs showing an articulating spacer dislocation. B , Revision spacer exchange to a static spacer created with antibiotic cement and intramedullary placement of an external fixator bar. Copyright © Wolters Kluwer, Inc. Unauthorized reproduction of the content is prohibited. 2023 B

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A

B

FIGURE 4

A and B , AP and Lateral radiographs of a low-friction articulating knee spacer created with primary total knee arthroplasty components, including a metal femur and an all-polyethylene tibia. This spacer has intramedullary dowels secured using Steinmann pins.

1,016 spacers, metal-on-polyethylene spacers had an increased range of motion, fewer spacer-specific com plications, and no spacer fractures compared with the four other spacer types. There was no difference in

terms of reinfection rates or difficulty with reimplanta tion between spacers. 32 Another systematic review of 48 reports comparing 962 articulating and 707 static spacers with mean follow-up of 4 years found both groups had similar Knee Society Scores, reinfection rates, complica tion rates, or reoperation rates. 33 However, the articulat ing spacer group had improved range of motion.

Section 4: Prosthetic Joint Infections

FIGURE 5 Radiograph from a patient who underwent revision to a nonarticulating Girdlestone spacer because of persistent infection with an articulating spacer. FIGURE 6 Radiograph of a low-friction spacer made with primary total hip arthroplasty components and high antibiotic- laden cement. Copyright © Wolters Kluwer, Inc. Unauthorized reproduction of the content is prohibited. 2023

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Chapter 16: Surgical Treatment of Hip and Knee Prosthetic Joint Infections

Spacer complications do occur. A 2019 study reported that, in a group of patients with varying types of hip spac ers, 48 of 185 patients (26%) were reported to have spacer complications. 34 Dislocation occurred in 17 patients (9%) and was associated with reduced femoral offset of greater than 5 mm and increased bone loss. Spacer fracture occurred in 14 of 185 patients (8%), 12% (12 of 97 patients) of molded versus 8% (2 of 23 patients) of handmade spacers. Periprosthetic fracture was associated with the use of an extended trochanteric osteotomy and increased offset greater than 5 mm. Stage Two Most patients receive 4 to 6 weeks of intravenous antibiotics after resection of the infected prosthesis. Reimplantation is delayed until the soft tissues have healed and the infection is treated. As of 2019, there was no consensus on the timing of reimplantation, 35 with some surgeons opting for a 2- to 6-week antibiotics holiday. The rationale for this is to allow for the emer gence of persistent infection before reimplantation. The 2018 ICM guidelines report limited evidence to support the use of an antibiotic holiday before reimplantation. 36 Although the Musculoskeletal Infection Society (MSIS) guidelines are very helpful in diagnosing PJI, they are not useful in the determination of persistent infection before reimplantation. 37 Serum erythrocyte sedimentation rate and C-reactive protein level are com monly assessed; however, they have a low sensitivity in this setting. 38 Declining serum erythrocyte sedimentation rate and C-reactive protein level are inferred to indicate appropriate response to treatment of the infection, 36 although this no association was shown with risk for reinfection. 39,40 Therefore, surgeons do not need to wait for these markers to normalize before reimplantation. 36 Synovial fluid analysis, reported in 2022, has also vary ing results, with white blood cell count and polymor phonuclear leukocyte percentage demonstrating high specificity (95%) and poor sensitivity (21%) in predicting persistent infection. 41 The synovial biomarker alpha- defensin has also shown poor sensitivity (7%) and poor overall accuracy (73%; area under the curve = 0.5) in detecting infection control with spacers. 42,43 Frozen sec tion and leukocyte esterase are two intraoperative metrics that are available. The utility of frozen section during the second-stage surgery has been debated. Original studies demonstrated that frozen section correlated with stan dard histology and had sensitivity, specificity, positive predictive value, and negative predictive values of 25%, 98%, 50%, and 95%, respectively. 44,45 Another analysis demonstrated the five neutrophils per high-power field method to have a high specificity (98%) and positive predictive value but a low sensitivity (28%). 46 Therefore, the test has limited benefit in this setting. Leukocyte

esterase is an appealing test as it is both quickly attain able intraoperatively and inexpensive. This test showed promising results in 2022, with a sensitivity, specificity, positive predictive value, and negative predictive value

of 82%, 99%, 90%, and 97%, respectively. 47 Outcomes Following Two-Stage Revision

Outcomes following two-stage revision arthroplasty as treatment for chronic PJI can be very successful. Several studies report 90% treatment success at 2-year follow-up and 80% to 90% at 5- to 10-year follow-up. 48 However, reports are highly variable and need to be taken in the context of the individual treatment protocols and defi nition of success. 49 A 2019 publication from the MSIS workgroup details tiers of outcomes to better differen tiate in the literature: (1) infection control with no con tinued antibiotics, (2) infection control with continued antibiotics, (3) need for revision surgery (with subgroups based on the type of surgical procedure), and (4) death (due to infection or not). 50 Many preoperative factors are associated with treat ment failure. A review of 108 two-stage revision TKAs for infection with 16 treatment failures analyzed 31 risk factors to identify associations with treatment failure. 48 Overall treatment success was 91% at 2 years, and mul tivariate analysis revealed four potential risk factors that may predict treatment failure: body mass index of 30 kg/m 2 or greater, surgical time greater than 4 hours, gout, and the presence of Enterococcus species during resection arthroplasty. Other studies demonstrated that body mass index greater than 40 kg/m 2 is associated with three- to fivefold increase in reinfection, revision, and reoperation rates. 51,52 Similar to all PJI treatment strategies, a two-stage revision also has a higher failure rate when infection with antibiotic-resistant organisms occurs. In 37 patients with PJI due to resistant organisms, 9 (24%) experienced reinfection, but only 4 (14%) were infected with the original organism. 53

Section 4: Prosthetic Joint Infections

One relative indication for two-stage revision for PJI is a previous failed surgery for infection, and this con tinues to be researched. In a retrospective review of 45 patients who have undergone two or more two-stage revision TKA for PJI, failure rates were compared using a PJI grading system 54 that accounts for host grade and extremity compromising factors. 55 Uncompromised hosts (MSIS type A) with an acceptable wound (MSIS type 1 or 2) had treatment success with 7 of 10 hosts, whereas type B2 hosts had success with 10 of 20, and type C3 had no treatment success with 2 hosts. This illustrates the importance of host factors in the treatment of PJI, and salvage strategies should be considered for those more compromised hosts that have a high likelihood for failure. Another study reported poor outcomes following a second attempt at two-stage treatment for recurrent PJI. Copyright © Wolters Kluwer, Inc. Unauthorized reproduction of the content is prohibited. 2023

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