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Management of Periprosthetic Joint Infections (PJIs)

Management of Periprosthetic Joint Infections (PJIs)

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Management of Periprosthetic Joint Infections (PJIs)

603 pages
Oct 25, 2016


Management of Periprosthetic Joint Infections (PJIs): Management of PJIs discusses periprosthetic joint infection (PJI), a fairly rare occurrence that is nonetheless one of the most serious complications in joint replacement surgery. Intricate interactions between the pathogen, the host, and the implant can result in PJIs which are not only physically devastating for the patient, but also financially crippling for health authorities and insurance companies.

Actions taken to minimize the risk of PJIs can be extremely challenging for the orthopaedic community. Consequently, new research, which is detailed in this comprehensive book, is being undertaken to minimize and manage these challenging infections.

  • Provides essential background knowledge on the mechanisms and identification of PJIs
  • Dedicated chapters focus on the complex, but vital eccentricities between PJIs in different areas of the body
  • Contains contributions from a mixture of clinical and academic experts in the field, thus ensuring balanced coverage
Oct 25, 2016

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Management of Periprosthetic Joint Infections (PJIs) - Elsevier Science

Management of Periprosthetic Joint Infections (PJIs)

First Edition

J.J. Chris Arts

Jan Geurts

Table of Contents

Cover image

Title page


List of contributors


Part One: Fundamentals of periprosthetic joint infections

1: Prevention of joint infections


1.1 Introduction

1.2 Preoperative considerations

1.3 Prevention of infection in the perioperative period

1.4 Prevention of infection after arthroplasty

1.5 Conclusions and future trends

2: Biofilm formation and the biological response


2.1 Introduction

2.2 Biofilm formation

2.3 Resistance to antimicrobial agents

2.4 Host response against biofilm

2.5 Clinical significance of biofilm

2.6 Therapeutic strategies against biofilm

2.7 Future trends

3: Biomaterials in treatment of orthopedic infections


3.1 Orthopedic implant-related infections

3.2 Biomaterials

3.3 Latest clinical evidence treatment osteomyelitis

3.4 Summary

4: S53P4 bioactive glass


4.1 Introduction

4.2 Working mechanism

4.3 Antibacterial effects

4.4 Effect on angiogenesis

4.5 Current clinical applications

5: Experimental models in orthopedic infection research


5.1 Osteomyelitis

5.2 Prostheses, osteosynthesis, and infection

5.3 Treatment

5.4 Infection development and prevention

5.5 Experimental models for orthopedic infections

5.6 Scoring of orthopedic infections in experimental models—(semi) systemic parameters

5.7 Scoring of orthopedic infections in experimental models—imaging and histology

5.8 Concluding remarks

Part Two: Types of periprosthetic joint infections

6: Periprosthetic infection in the hip joint


6.1 Introduction

6.2 Definition

6.3 Classification

6.4 Causative organisms

6.5 Diagnosis

6.6 Other new diagnostic tools

6.7 Management

6.8 Management of periprosthetic fracture in the presence of chronic PJI

6.9 The eradication of biofilm: Goals for the future

6.10 Conclusion

7: Infection in total knee arthroplasty


7.1 Total knee arthroplasty today

7.2 Infection risks and prevention

7.3 Diagnosis

7.4 Chronic TKA infection

7.5 Management of the infected TKA

7.6 One-stage revision

7.7 Two-stage revision

7.8 Outcomes

7.9 Knee arthrodesis

7.10 Complications

8: Periprosthetic infection in shoulder and elbow joints


8.1 Introduction

8.2 Clinical presentation

8.3 Diagnostic testing

8.4 Treatment and outcomes—Shoulder

8.5 Treatment and outcomes—Elbow

8.6 Conclusion and future directions

Part Three: Managing and treating periprosthetic joint infections

9: Practice and guidelines for treating periprosthetic joint infections: Single- and two-stage revision


9.1 Introduction

9.2 Patient preparation, implant removal, and surgical debridement

9.3 Analysis of results

9.4 Conclusions and future trends

10: PMMA beads and spacers for local antibiotic administration


10.1 History

10.2 Rationale and pharmacokinetics of antibiotic-loaded PMMA

10.3 Beads

10.4 Spacers

11: Pathogen-directed antibiotic therapy


11.1 Introduction

11.2 Cultures and diagnosis

11.3 Prophylaxis and empirical therapy

11.4 The pathogens in PJI

11.5 The antibiotics

11.6 Pathogen-directed choice

11.7 Conclusion and areas for further research

Part Four: Case studies

12: Imaging of prosthetic joint infections


12.1 Introduction

12.2 Conventional imaging

12.3 Nuclear imaging

12.4 Imaging in the assessment of PJI



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This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein).


Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary.

Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility.

To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein.

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A catalogue record for this book is available from the British Library

ISBN: 978-0-08-100205-6 (print)

ISBN: 978-0-08-100242-1 (online)

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List of contributors

S. Alazzawi     The Royal London Hospital, London, United Kingdom

M.H. Amini     Cleveland Clinic, ​Orthopaedic and Rheumatologic Institute, Cleveland, OH, United States

J.J. Arts

Maastricht University Medical Centre, Maastricht

Eindhoven University of Technology, Eindhoven, The Netherlands

B.D. Brause

Hospital for Special Surgery

Weill Cornell Medical Center, New York, NY, United States

L. Drago

IRCCS Galeazzi Institute

University of Milan, Milan, Italy

M.B. Ekkelenkamp     University Medical Center Utrecht, Utrecht, The Netherlands

P.J. Evans     Cleveland Clinic, ​Orthopaedic and Rheumatologic Institute, Cleveland, OH, United States

D. George     University College London Hospitals, London, United Kingdom

J.A.P. Geurts     Maastricht University Medical Center, Maastricht, The Netherlands

F.S. Haddad

Institute of Sport, Exercise and Health

University College Hospital, London, United Kingdom

M.W. Henry

Hospital for Special Surgery

Weill Cornell Medical Center, New York, NY, United States

D.J. Hulsen     Maastricht University Medical Centre, Maastricht, The Netherlands

O. Khan     Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom

N.C. Lindfors     University of Helsinki, Helsinki, Finland

N. Logoluso     Orthopaedic Research Institute Galeazzi, Milan, Italy

K.N. Malizos     University of Thessaly, Medical School, Biopolis, Larissa, Greece

G. Manzi     CHU Rennes, Rennes, France

A.O. Miller

Hospital for Special Surgery

Weill Cornell Medical Center, New York, NY, United States

J.C.E. Odekerken

Maastricht University Medical Centre, Maastricht

Zuyd University of Applied Sciences, Heerlen, The Netherlands

L.L. Reubsaet     University Medical Center Utrecht, Utrecht, The Netherlands

E.T. Ricchetti

Cleveland Clinic, ​Orthopaedic and Rheumatologic Institute

Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, United States

C.L. Romanò     Orthopaedic Research Institute Galeazzi, Milan, Italy

S. Scarponi     Orthopaedic Research Institute Galeazzi, Milan, Italy

O.P.P. Temmerman     NWZ, Centre for Orthopaedic Research (CORAL), Alkmaar, The Netherlands

M. Toscano

IRCCS Galeazzi Institute

University of Milan, Milan, Italy

N.A. van Gestel     Eindhoven University of Technology, Eindhoven, The Netherlands

T.A. van Vugt     Maastricht University Medical Centre, Maastricht, The Netherlands

S.E. Varitimidis     University of Thessaly, Medical School, Biopolis, Larissa, Greece

S.J. Verberne     NWZ, Centre for Orthopaedic Research (CORAL), Alkmaar, The Netherlands

G.H.I.M. Walenkamp     Maastricht University Medical Center, Maastricht, The Netherlands

T.J. Welting     Maastricht University Medical Centre, Maastricht, The Netherlands


This book summarizes Management of Periprosthetic Joint Infections (PJIs) from fundamental aspects on prevention and diagnostics to surgical and pathogen-directed antibiotic treatment concepts. Furthermore, attention is placed on the biofilm biological response, biomaterials for treatment of orthopedic infections, and on experimental models in orthopedic infection research.

The primary reason for the compilation of this book is the fact that there is high and multidisciplinary interest in PJIs and osteomyelitis treatment. As clinical lecturers, we have been confronted with a lot of interest in this topic over the years, but unable to find an adequate summary of these topics directed toward clinical implementation for a multidisciplinary audience.

This book is by no means intended as a comprehensive overview but aims to raise awareness and stimulation of discussion regarding Management of Periprosthetic Joint Infections in clinical practice.

We believe it will present a useful and practical addition to your clinical practice and education.

Sincerely yours,

Chris Arts; Jan Geurts editors

Part One

Fundamentals of periprosthetic joint infections


Prevention of joint infections

A.O. Miller*,†; M.W. Henry*,†; B.D. Brause*,†    * Hospital for Special Surgery, New York, NY, United States

† Weill Cornell Medical Center, New York, NY, United States


Prosthetic joint infection (PJI) is morbid, costly, and increasingly common due to the large number of patients with indwelling joint prostheses. Although some patients present with unmodifiable factors which increase their individual risk of infection, there are a variety of pre-, peri-, intra-, and postoperative factors which can be optimized to decrease the risk of this unfortunate complication. These include: (1) the underlying health and nutritional status of the patient, (2) the provision of adequate topical and perioperative antisepsis, (3) intraoperative best practices, (4) consideration of postoperative risks, (5) complications of wound healing, and (6) dental infection and dental care. Considerable controversy exists regarding many of these factors. This chapter reviews the important risk factors to provide concise and practical recommendations regarding the prevention of PJI.


Prosthetic joint infection; Infection prevention; Surgical site infection; Risk factors; Quality improvement.

1.1 Introduction

Modern arthroplasty techniques improve the mobility and the quality of life of more than one million inhabitants of the United States of America each year: in 2012, 452,000 hip and 671,000 knee arthroplasties were performed [1]. Prosthetic joint infection (PJI) is a feared complication of arthroplasty. Population incidence of PJI in developed countries has been estimated in the range of 1–2% in the first two postoperative years, with lower rates thereafter [2–5]. Incidence varies substantially across medical facilities [6]. PJIs are costly in terms of individual patients’ health and expenses, legal considerations, and costs to health care systems and third parties. Economically, an individual hip PJI costs the average patient $30,000–120,000 [7–9], with projected current cumulative US national costs up to $1 billion. Infection can lead to losses in mobility, medical complications of the infection and its therapy, decreased quality of life, and loss of life. Given the annual increases in arthroplasty volume due to improved access to surgery and marked growth in target populations, strategies to prevent PJI are critical. Aiming to eliminate this dreaded complication is worthwhile, even if we cannot achieve a zero-percent infection rate.

This chapter reviews many presently available approaches to preventing PJI and some promising future avenues. Much of our understanding of PJI prevention (and management) has been made in the absence of randomized prospective studies. Indeed, there is substantial practice variability between and within medical centers worldwide. We attempt to highlight areas where well-controlled studies show significant advantages of one strategy over others, and other areas where significant controversy remains. While guidelines and consensus documents addressing PJI generally reflect available science and expertise [10,11], the management of these difficult cases ultimately depends on clinicians and patients coming to individualized decisions based on the specifics of each individual case.

1.2 Preoperative considerations

1.2.1 Preoperative patient selection and risk factors for infection

Over decades of technical improvement, arthroplasty has become available to increasingly complex groups of patients. Comorbidities powerfully alter infection risk, so careful preoperative selection and optimization of arthroplasty candidates is critical. Comorbidities are grossly categorized into modifiable and nonmodifiable risks. Modifiable risks include active infection, active tobacco use, and uncontrolled diabetes. Nonmodifiable risks cannot be altered preoperatively and include prior same-site surgery, prior infection, preexisting foreign material, and age. In this categorization scheme, a substantial middle ground exists, as in the cases of diabetes and autoimmune disease, where the underlying disease may elicit a nonmodifiable increase in infection risk, which is further increased by the intensity of therapy given (for autoimmune diseases) or not (for diabetes). Nevertheless, this organizational structure helps in stratifying risk and in optimizing suitable patients for arthroplasty.

1.2.2 Nonmodifiable comorbidities

Revision arthroplasty, compared to primary arthroplasty, has a higher rate of PJI [12,13]. Likewise, prior nonarthroplasty surgery at the site of primary arthroplasty increases the risk of PJI; this observation is likely linked to the fact that posttraumatic arthritis is associated with PJI [14–16]. Prior same site PJI and increased surgical duration also increase the risk of PJI. Likely etiologic factors include changes in the local wound matrix (slow healing, impaired vascular flow, abnormal regulation of surface microbe ecology), underlying host immune factors predisposing to infection, and subclinical (unrecognized) persistent infection.

1.2.3 Modifiable comorbidities Active pyogenic infections

Generally, treatable active infections should prompt delay in elective arthroplasty until resolved. Elective arthroplasty is contraindicated in the presence of active intraarticular infection. Distantly (> 10 years) treated native infection may not confer risk for PJI [17]. Early experience in the revision of infected joint arthroplasties noted a high rate of recurrent infection requiring arthrodesis or excision of the joint [18–20]. In the present era, routine elective arthroplasty is not performed in the setting of known intraarticular infection, and when evidence of infection is incidentally encountered intraoperatively, individualized surgical decisions (often postponing implantation of the prosthesis to a later date) must be made.

The presence of skin and soft tissue infections at or near the site of surgery is likely to increase the risk of PJI, via impairment in wound healing of the infected integument and via the potential for contiguous seeding of the prosthesis. The presence of bacteremia, and infections associated with bacteremia (i.e., dental abscesses, endovascular infections, pyelonephritis), is a risk factor for PJI [21,22]. Because vascular supply to the healing bone after arthroplasty is enhanced for approximately 2 years, the risk of bacteremic seeding appears to be to be inversely proportional to the age of the prosthesis. This risk is likely highest immediately after elective arthroplasty.

Acute nonorthopedic infections requiring antimicrobials (pharyngitis, sinus infections, pneumonia, symptomatic urinary tract infection) and significant acute viral infections (including herpes zoster and influenza) usually lead to short-term postponement of surgery, pending resolution. Colonization with Staphylococcus aureus

At any given moment, one-third of the global population is colonized with Staphylococcus aureus, whether resistant (MRSA, 2–4%) or sensitive (MSSA, 30–40%) to methicillin [23,24]. This colonization state is not associated with high likelihood of illness in the typical human host. In the surgical patient, however, alterations in the skin integrity can lead to inoculation of S. aureus (and other colonizing skin flora) into vulnerable zones. Some evidence suggests that patients colonized with S. aureus are likelier to have surgical site infections (SSIs) and nosocomial infections (e.g., [25–27]). There may be an important threshold quantity of colonizing staphylococci above which risk is increased. The number of organisms needed to establish infection is substantially decreased by the presence of indwelling metallic foreign bodies.

Multiple studies have evaluated decolonization strategies. Blanket decolonization of ICU patients led to decreased nosocomial infection rates in one large study [28], but not all studies have shown a positive association (i.e., [29]), and resistance to topical antiseptics in the setting of routine use remains a concern [30]. Furthermore, the cost-effectiveness of universal screening is not certain [31]. Whether or not the benefits of screening patients for S. aureus prior to arthroplasty outweigh the costs and inconveniences remains unclear. To date, no major expert group recommends universal screening and decolonization.

The strategy used at our institution involves selective screening of high-risk patients, including patients with prior history of staphylococcal infection. Swabs of the anterior nares, pharynx, axillae, and groin are obtained. Patients found to have S. aureus skin carriage undergoes decolonization with 10 applications of mupirocin to the nostrils and five applications of chlorhexidine 4% liquid solution from chin to feet, over the 5 days preceding surgery. Oral antibiotics (usually trimethoprim-sulfamethoxazole plus rifampin) are sometimes added during this time, as reported in other literature [32]. Decolonization is neither necessarily absolute nor long lasting: the goal is to decrease the burden of potential pathogens on the skin and the nose during the intra- and postoperative periods during which the patient is at maximal risk of infection.

Controversy regarding proper management of arthroplasty patients preoperatively colonized with S. aureus continues. Whether or not targeted or universal screening is efficacious, which screening test is optimal, and what treatment strategies (if any) work best remain important unresolved questions. Hyperglycemia and diabetes

Hyperglycemia decreases phagocyte function and is a risk factor for nosocomial complications in many medical arenas. In various nonorthopedic areas of acute medical care, strict control of hyperglycemia has been variably associated with improved outcomes, and protocols vary greatly [33]. Preoperative hyperglycemia (generally defined as fasting glucose > 180 mg/dL) is associated with PJI [34], and postoperative morning hyperglycemia may be an even better predictor of PJI [34,35]. Diabetes mellitus may be an important (nonmodifiable) risk factor, independent of the degree of disease control [36]. At our institution, a dedicated team headed by an endocrinologist helps optimize perioperative hyperglycemia, while elective surgeries are postponed for patients with glycosylated hemoglobin A1c (HbA1c) > 9 mg/dL with the goal of setting 8% as the new threshold in the near future. Dental disease

Odontogenic bacteremia is commonplace, particularly in the elderly with periodontal disease, but dentogingival bacteria are only occasional causes of late hematogenous PJI. There has been long-standing debate regarding the need for antimicrobial prophylaxis when arthroplasty patients undergo dental procedures (briefly discussed later). There is little data to support the efficacy of preoperative dental clearance in routine arthroplasty [22,37]. In our institution, the majority of patients are screened for severe dental issues during preoperative medical clearance, but formal clearance from a dentist is not generally required. Most importantly, the presence of focal dentogingival pain or infection must be resolved prior to elective arthroplasty. Immunosuppression and autoimmune/rheumatologic disease

Patient with autoimmune diseases have an increased incidence of joint disorders requiring arthroplasty and frequently received immunomodulatory medications. Both the underlying diseases and their therapies can further predispose to anatomic abnormalities increasing the risk of infection. It is unclear which factors are most important, but the risk of surgical infection in such patients is increased [15,38,39].

In many patients with immunodeficiency, medications can be modified to reduce infection risk in the perioperative period, with input from the rheumatologist, transplant specialist, or hematologist-oncologist. At our institution, perioperative protocols guiding the management of a variety of immunosuppressive medications have been developed, although they typically require individualization based on the severity and specifics of the underlying illness. Generally, disease-modifying agents are withheld prior to elective arthroplasty (at a time related to their half-life) and restarted when wound healing has progressed satisfactorily. Human immunodeficiency virus (HIV)

The majority of current arthroplasty patients with HIV are successfully treated with highly active antiretroviral medications (HAART); a reasonable expectation for these patients is an undetectable HIV viral load and a stable CD4 count substantially above 200. HIV infection does not appear to be a very strong risk factor for PJI. In HIV-positive hemophiliac populations prior to the HAART era, HIV was not associated with PJI risk. More recent studies confirm that HIV-positive arthroplasty patients with undetectable viral load and CD4 count greater than 200 have a risk profile similar to HIV-negative patients [40,41]. In one recent population-level study, patients with HIV were at slightly higher risk of postoperative wound infection, attributable to HIV’s associated comorbidities; HIV itself was not an independent risk factor [42]. In our institution, HIV-positive candidates are generally cleared for elective arthroplasty when they have optimized their immunologic and virologic control on highly active antiretroviral therapy, generally in cooperation with their primary HIV provider. Obesity and malnutrition

Obesity is associated with increased risk of PJI, via multiple mechanisms including concurrent medical comorbidities, impaired wound healing, and increased surgical duration [43,44]. Obesity is also a major driver of joint pain and arthritis. Weight loss associated with bariatric surgery has been reported to significantly improve knee complaints [45]. Short-term weight loss before arthroplasty may not measurably modify risk [46]. The morbidly obese patient needs to be counseled about the increased risks of perioperative complications including infection: a BMI > 40 appears to be a cutoff above which the risk of perioperative complications is markedly elevated [47,48].

Malnutrition, a broad term intended to capture the presence of any and all nutritional deficiencies, is a separate phenomenon which is prevalent throughout the population. Variable clinical definitions of malnutrition, and the high frequency of confounding comorbidities in malnourished patients, complicate the study of its effects on surgical outcomes. There may be no better general test of nutritional status than careful clinical interview and physical examination. Various studies confirm the plausible hypothesis that malnourishment is associated with adverse surgical outcomes in arthroplasty (for instance, Refs. [49,50]). Hypoalbuminemia may be a more useful predictor of PJI and other perioperative complications than morbid obesity [51], but no single preoperative test has been found to be sensitive and specific for malnourishment. Postoperative monitoring (or replacement) of albumin is not routine practice in our institution. We believe that accurate weight measurements should be taken at every visit in an attempt to heighten the importance of nutrition and body weight as predictors of surgical, and overall health, outcomes.

Optimal strategies for improving preoperative nutritional status remain unclear. Referrals for outpatient nutrition counseling prior to elective arthroplasty may be variably associated with measurable short-term outcomes, but the surgical period may be a moment of opportunity during which positive overall health practices can be adopted, reducing the long-term health risks of malnutrition and obesity. The efficacy of carbohydrate loading immediately before surgery remains in question [52]. Integumentary alterations

There is little literature to guide the surgeon regarding the safety of arthroplasty when there is an active ulceration, lesion, or infection in the vicinity of the operative site. However, it is well documented that skin conditions such as chronic venous ulceration, psoriasis, and eczema develop altered microbiological flora, with increased colonization with more pathogenic bacteria such as Pseudomonas aeruginosa and S. aureus [53–55]. Prospective studies of nonorthopedic patients reveal skin ulceration to be a serious risk factor for SSI [56]; elective arthroplasty should not be performed in this setting. Small retrospective studies demonstrate increased rates of both postoperative wound infections and PJI in patient with active psoriasis when compared to healthy historical controls [57,58]. Active skin disease or ulcerations near the planned operative site should be treated aggressively to mitigate the risk of postoperative infection.

Venous stasis, lymphedema, and dermatologic disorders variably increase PJI risk by altering the wound healing potential, as well as the microbiology, of the surgical wound. Venous stasis and lymphedema are commonplace in the arthroplasty population and are never wholly reversible. However, compression stockings, elevation of the affected extremity, and careful preoperative fluid management can optimize symptom severity. Tobacco, Ethanol, and intravenous drug use

Perioperative smoking cessation improves surgical outcomes (e.g., Refs. [59,60]). In addition, there is a dose-dependent effect of tobacco smoke on surgical outcomes; among smokers, consumption of more than one pack of cigarettes daily may confer a higher risk of hip arthroplasty surgical complications [61]. Although progressively shorter periods of preoperative tobacco cessation are associated with rising rates of surgical complications, it is likely that quitting at any time during the preoperative period is always better than continued tobacco use. Preoperative smoking cessation programs have been shown to lower risk of surgical complications including infection [62] but are not common at most institutions.

Although moderate alcohol use has been associated with improved survival in population studies, excessive alcohol use obviously confers health risks, not surprisingly including surgical infections [63,64]. The mechanisms involved are likely multifactorial, including social and behavioral comorbidities, preexisting nutritional deficits, the stresses of inpatient alcohol withdrawal, and direct effects of alcohol on neutrophils and other immune effectors. Evidence-based cutoffs for excessive alcohol use do not exist, but it is likely that screening and recommendations to reduce or cease consumption in patients consuming larger amounts of alcohol decrease PJI risk.

Intravenous drug use (IVDA) is strongly associated with development of PJI; incidence rates exceeding 25% have been consistently observed [65–67]. Intravenous drug use is frequently associated with bacteremia directly related to contaminated injection techniques, and users are prone to a broad range of bacterial and fungal infections, most commonly S. aureus. We believe IVDA to be an absolute contraindication to elective arthroplasty. Preoperative urinary screening and management of bacteriuria

The literature regarding the contribution of asymptomatic bacteriuria (ASB) to the risk of infectious complications following surgery is neither voluminous nor robust. Catheterization of the bladder is routine in most anesthesia protocols and has been associated with transient bacteremia in the setting of asymptomatic bacteriuria [68]. Of the available published studies, however, no correlation between ASB and SSI or PJI has ever clearly been demonstrated [69,70]. These studies, however, are limited by their lack of power and by their primarily retrospective design. A recent prospective multicenter observational cohort study of nearly 2500 patients found that although ASB was an independent risk factor for PJI, there was no correlation between the microbiological causes of the ASB and the PJI [71]. In addition, preoperative treatment of ASB was not associated with a decrease in PJI. These findings suggest that ASB may be a marker of PJI risk, but not a direct cause of PJI. Currently, there are no formal guidelines on the management of ASB prior to orthopedic surgery although several experts in the field recommend proceeding with arthroplasty in the setting of ASB as long as routine prophylactic antibiotics are given (e.g., [72]). Given this lack of correlation between ASB and postoperative infection, the practice of obtaining routine urinalyses in asymptomatic patients undergoing arthroplasty is likely unwarranted [73].

1.3 Prevention of infection in the perioperative period

1.3.1 Body cleansing at home in anticipation of surgery

Patient-directed antiseptic treatment starting the night before surgery is a commonly employed practice to reduce the incidence of SSI. Routine preoperative showering with chlorhexidine gluconate (CHG) solution or antiseptic soap is part of the preoperative instructions for many types of elective surgery, including arthroplasty. Like many such measures that intuitively appear to be rational and medically sound interventions, there is very little published literature showing any benefit. There has also been no standardization of the cleansing regimen recommended. A large metaanalysis of data from multiple randomized controlled trials of patients undergoing a wide range of surgery by the Cochrane Group did not find the incidence of SSI to be lower in patients undergoing showering with CHG vs patients not showering or in patients showering with placebo [74]. Several observational prospective studies of patients specifically undergoing arthroplasty, however, did report a reduction in the incidence of SSI in patients using CHG wipes, though the results from these studies did not achieve statistical significance [75,76]. Regardless of these findings, preoperative showering or self-cleansing by patients is a common practice at many institutions.

1.3.2 Preoperative hair management

Current SHEA guidelines for the prevention of SSI recommend against elective hair removal except when the presence of hair will interfere with the operation [77]. When hair removal is considered necessary, clippers or a depilatory agent is recommended. Use of a razor to remove hair is associated with an increased risk of SSI. Patients should be advised not to shave the legs or other operative sites for several days prior to and following prosthesis implantation. The timing of hair removal is also critical to lower the risks of infection; the lowest rates of infection are observed when hair removal is done just prior to surgery.

1.3.3 Perioperative antibiotics

The use of perioperative antibiotics is an integral part of the measures taken to reduce the incidence of SSI in almost all fields of surgery, and orthopedic surgery is no exception. In addition to the extended length of stay and cost associated with treatment of orthopedic postoperative infections, SSI is also a significant risk factor for the development of prosthesis-related infections and can lead to considerable morbidity [78]. The use of intravenous antibiotics to prevent SSI is recommended for spinal surgery, repair of closed fractures, implantation of any orthopedic fixation device, and arthroplasty [79]. Antibiotic prophylaxis is not indicated in clean procedures involving the hand, knee, or foot with no implantation of foreign material.

In order to be effective, the appropriate antibiotic must be given with careful attention to timing and dose, as well as patient factors, including allergies, renal function, and weight [80]. Cefazolin is the recommended first line agent for orthopedic surgery. In the setting of allergy to cephalosporins, vancomycin or clindamycin can be used as alternatives. Although the frequency of specific bacteria causing PJI varies by the site of arthroplasty [81], there are no recommendations to adjust the antibiotic selection based on the surgical site.

Broader-spectrum preoperative antibiotic prophylaxis is not indicated in patients with poorly controlled diabetes, or who are otherwise immunosuppressed, despite their increased risk for postoperative infectious complications. However, there are certain comorbidities that should prompt adjustments to the antibiotic prophylaxis chosen for a given patient. Vancomycin should be used in patients known to be colonized with MRSA or when the patient is at high risk for MRSA in the absence of microbiologic data [79]. There is a growing body of evidence to suggest that the dual use of cefazolin and vancomycin in patients colonized or at risk of colonization with MRSA is more effective that with MRSA alone, but this has not been included in any formal recommendations [82,83]. In addition, vancomycin can be used if a true outbreak of MRSA or methicillin-resistant coagulase-negative staphylococci has been detected within the institution. Although the management of SSI prevention in patients known to be colonized with multidrug-resistant organisms (e.g., vancomycin-resistant enterococci or carbapenem-resistant Enterobacteriaceae) is not well studied, it seems reasonable to expand the regimen used to target the organism of concern (in addition to covering the usual causes of PJI).

The timing and dosing of perioperative antibiotics are both critical in allowing adequate tissue concentrations to be achieved prior to the start of surgery. The American Association of Orthopedic Surgeons [84], the Center for Disease Control and Prevention [80], and the National Surgical Infection Prevention Project [85] suggest that doses be fully infused within 1 h of incision and prior to the application of any tourniquet. It is important to note that as the dose of vancomycin increases, the time of infusion correspondingly increases. When a proximal tourniquet is used, antibiotics must be fully administered before the tourniquet is inflated [86].

In cases exceeding two half-lives of the antibiotic or in cases with excessive blood loss (> 1500 ml; [79]) or fluid resuscitation (> 2000 ml; [72]), redosing of the antibiotic is required to maintain the concentration above the minimal inhibitory concentrations of the common causes of SSI.

The efficacy of a properly administered first dose of antibiotics has been shown in multiple well-conducted studies [87,88]. Likewise, these studies also demonstrate the decreasing utility of these antibiotics the longer they are continued following wound closure. Numerous guidelines, including those from the Surgical Infection Society, SCIP, AAOS, and SHEA/IDSA, all recommend the discontinuation of prophylactic antibiotics within 24 h of the end of surgery. Postoperative antibiotic prophylaxis in patients with indwelling drains or persistent wound drainage is not recommended.

1.3.4 Surgical skin preparation

Preoperative skin preparation with an antiseptic is a critical intervention reducing incidence of postoperative wound infections. Contamination of the prosthesis at the time of surgery is a significant cause of PJI. The most common agents are chlorhexidine gluconate, iodophors, and alcohol-containing combination products; the current CDC guidelines for the prevention of SSI do not recommend any of these agents above any other [80]. Studies comparing these agents have been equivocal as to which is superior. The largest multicenter prospective trial to date comparing methods of surgical site antisepsis in 849 patients undergoing clean-contaminated cases, primarily intraabdominal surgery, found the use of CHG with alcohol to be superior to povidone-iodine (without alcohol; [89]). A large prospective single-center sequential implementation trial compared three preoperative skin preparations in 3209 patients; chlorhexidine/isopropyl alcohol, iodine povacrylex in isopropyl alcohol, and two applications of povidone-iodine separated by an application of isopropyl alcohol. The lowest infection rate was seen in the iodine povacrylex in the isopropyl alcohol arm, but both iodophor groups achieved better outcomes than the chlorhexidine arm, with statistical significance [90].

There have been no prospective trials of surgical site skin preparation in patients undergoing arthroplasty. However, based on the available literature, there may be an advantage to alcohol-based skin antisepsis, with chlorhexidine or iodophors. One disadvantage of alcohol solutions is the risk of operating room fires [91]. Antiseptic skin preparation is never perfect because bacteria also reside within skin structures including hair follicles, sebaceous cysts, and epidermis [92–94].

1.3.5 Antibiotic-loaded bone cement (ALBC) prophylaxis in primary and revision arthroplasty

The benefit of antibiotic-loaded bone cement (ALBC) prophylaxis in primary arthroplasty remains uncertain. There is considerable concern regarding the use of prophylaxis with ALBC in the current era of very low infection rates, especially when the disadvantages accompanying routine ALBC use may outweigh any potential benefit. In prospective randomized studies, there was no difference between the use of cefuroxime in ALBC and IV cephalosporin administration [95]. In addition, cephalosporins are too potentially allergic for routine use in ALBC. Using gentamicin in ALBC compared with IV

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