Abstract
Abstract
Peri-prosthetic joint infection (PJI) is a serious complication of prosthetic joint arthroplasty. A better understanding and reversal of modifiable risk factors may lead to a reduction in the incidence of incisional (superficial and deep) and organ/space (e.g., PJI) surgical site infections (SSI). Recently, the Centers for Disease Control and Prevention (CDC) and the Healthcare Infection Control Practices Advisory Committee (HICPAC) published the Guideline for Prevention of Surgical Site Infection. This targeted update applies evidence-based methodology in drafting recommendations for potential strategies to reduce the risk of SSI both across surgical procedures and specifically in prosthetic joint arthroplasty. A panel of PJI content experts identified nine PJI prevention research opportunities based on both evidence gaps identified through the guideline development process (transfusion, immunosuppressive therapy, anticoagulation, orthopedic space suit, and biofilm) and expert opinion (anesthesia, operative room environment, glycemic control, and Staphylococcus aureus nasal screening and decolonization. This article offers a road map for PJI prevention research.
A
The Centers for Disease Control and Prevention (CDC) and the Healthcare Infection Control Practices Advisory Committee (HICPAC) recently published a targeted update to the Guideline for Prevention of Surgical Site Infection [7]. This update represents a transition from guideline recommendations based largely on expert opinion [8–10] to recommendations using a systematic, rigorous evidence-based approach [11]. This process involves performing a systematic review of the best available evidence and providing explicit links between the evidence and the resultant recommendations using the grading of recommendations assessment, development, and evaluation (GRADE) method [7,11].
The guideline is divided into a Core section with recommendations applicable across a broad spectrum of surgical procedures and a Prosthetic Joint Arthroplasty section. A search of the prosthetic joint arthroplasty specific SSI literature for randomized controlled trials (RCTS) and systematic reviews from 1998–July 2011 in four databases (Ovid-Medline,® PREM,® Embase,® and Cochrane®) revealed little to no high-level evidence for the selected topics. Thus, the literature search for this section was expanded to include controlled observational studies (OBS) and extended to December 2011.
The purpose of this article is to propose recommendations for priority PJI prevention research questions based on both evidence gaps identified during the guideline development process and additional questions proposed by content experts. The SSI prevention research opportunities specific to the Core section topics are addressed by general SSI prevention content experts in a separate article.
Identifying Peri-prosthetic Joint Infection Prevention Research Areas
The guideline Prosthetic Joint Arthroplasty section included six key topics: Peri-operative blood transfusion, systemic immunosuppressive therapy, anticoagulation, orthopedic space suit, post-operative antimicrobial prophylaxis duration with surgical drain use, and biofilm. Based on the CDC and HICPAC categorization scheme for recommendations, those “unresolved issues for which there was either low to very low-quality evidence with uncertain tradeoffs between benefits and harms or no published evidence on outcomes deemed critical to weighing the risks and benefits of a given intervention” were categorized as “No recommendation/unresolved issues” or for the purposes of this article “evidence gaps” [11]. The PJI content experts who participated in the guideline development process identified additional topics and questions not addressed in the guideline but which they also deemed priority PJI prevention research areas. Finally, the recommendations for research were further categorized according to the type of studies needed to address each question: Risk factors/epidemiologic research, intervention research, implementation research, and basic science research (Table 1).
Recommended Research Questions Based on Guideline Evidence Gaps
The research topics below are presented in the same order as in the CDC/HICPAC Guideline for Prevention of Surgical Site Infection. The first research question for each topic is considered that topic's critical research question.
1. Transfusion
i. Does the volume of blood transfusion (allogeneic or autologous) impact the risk of PJI? (Epidemiologic and Intervention research)
ii. Is there a specific patient population at increased risk of PJI with autologous donated blood transfusion? (Epidemiologic and Intervention research)
iii. Does the use of intra-operative cell savers or post-operative reinfusion systems impact the risk of PJI? (Epidemiologic and Intervention research)
iv. Do pre-operative supplemental iron and/or erythropoietin therapy reduce the risk of PJI? (Intervention research)
2. Immunosuppressive therapy
i. What is the optimal timing to discontinue biologic immunosuppressive therapy pre-operatively to reduce the risk of PJI? (Epidemiologic, Implementation, and Intervention research)
ii. What is the optimal timing to resume biologic immunosuppressive therapy post-operatively to reduce the risk of PJI? (Epidemiologic and Intervention research)
iii. How long after intra-articular corticosteroid injection should you postpone a surgical procedure to reduce the risk of PJI? (Epidemiologic and Intervention research)
3. Anticoagulation
i. Does the post-operative duration of anti-coagulation prophylaxis impact the risk of PJI? (Epidemiologic and Intervention research)
ii. What are the associated confounders (e.g. hematoma, other incision healing complications) between specific anti-coagulation agents and the risk of PJI? (Epidemiologic research)
4. Orthopedic space suit
i. Does wearing an orthopedic space suit impact the risk of PJI? If so, is the risk affected by the use of laminar airflow? (Intervention research)
ii. Which operating room (OR) personnel should wear an orthopedic space suit to reduce the risk of PJI? (Implementation and Epidemiologic research)
5. Biofilm
i. What is the impact of strategies to prevent biofilm formation on reducing the risk of PJI (e.g., vaccines, antimicrobial coated prostheses, antibiofilm agents [e.g., rip inhibitors], prosthesis surface modification [e.g., galvanic coupling, “printing” technologies, nanotechnology, etc])? (Basic science and Intervention research)
ii. Are there high-risk patient populations that might benefit from the addition of antibiotic loaded fixation cement in primary and revision arthroplasties? (Intervention research)
Additional Research Questions Proposed by Content Experts
Anesthesia, OR environment, S. aureus decolonization, and the related questions were suggested by the content experts early in the guideline development process but did not make the final cut as priority guideline topics. Glycemic control was addressed in the guideline Core section evaluating the evidence across surgical procedures. Here, the topic and questions are specific to PJI prevention.
1. Anesthesia
i. How do general and neuraxial anesthesia impact the risk of PJI via such pathways as reduced systemic exposure to possibly immunosuppressant anesthetic agents, or differences in tissue oxygen tension because of respiratory suppression? (Risk factor/Epidemiologic research)
2. Operating room environment
i. How does the density of bacterial counts in the OR air correlate with the risk of PJI? (Risk factor/Epidemiologic research)
ii. Does the number of OR personnel in the operating suite affect risk of PJI?
iii. What is the impact of OR ultraviolet radiation, high-efficiency particulate absorption filtration, and laminar flow on PJI rate? (Intervention research)
3. Glycemic control
i. How long should blood glucose be controlled post-operatively? What are the best strategies to achieve peri-operative blood glucose control in prosthetic joint arthroplasty patients (e.g., insulin sliding scale, continuous infusion, etc.)? (Epidemiologic and Intervention research)
ii. Is there an optimal pre-operative Hg A1C level associated with a reduced risk of PJI? (Epidemiologic and Intervention research)
4. S. aureus nasal screening and decolonization
i. Is pre-operative screening and decolonization for S. aureus effective in reducing the risk of PJI? If so, what are the best strategies for implementing a pre-operative S. aureus screening and decolonization program? (Epidemiologic and Intervention research)
ii. Are there any particular subgroups that would benefit the most from S. aureus screening and decolonization? (Epidemiologic and Intervention research)
Challenges and Opportunities
Answering some of the pressing questions related to prevention strategies should rely, when possible, on well-conducted RCTs. From the research questions above, we have identified nine critical research questions to address current gaps (Table 2). The historical barriers related to conducting RCTs in patients undergoing prosthetic joint arthroplasties are mostly logistical and in great part related to the large number of patients needed for these studies given the low rates of PJI (outcome of interest). 16 This has led previous investigators to adopt practices based on personal experience or low quality studies. Over time, these adopted practices became the standard of care, further hindering the ability to study the efficacy of several interventions.
The creation of more common and widely accepted surrogate markers related to the outcome of interest (PJI) such as sampling methods to determine the contaminating bioburden of the sterile field before skin closure, incision healing complications, incisional SSI, pain, or malfunction may reduce the number of patients needed in a RCT. Other questions might be better answered by conducting well-designed large, prospective, multi-center cohort studies, case control studies, or open randomized clinical trials. We believe that professional societies may be able to play a bigger role in coordinating this type of research. The focus on the creation of multi-center national registries of patients undergoing hip and knee arthroplasty in the United States is important in setting up the infrastructure needed to conduct these studies. This collaboration may lead to the standardization of risk factors and PJI definitions. We hope that the current article offers a road map that will lead to higher quality interventions and research.
Footnotes
Author Disclosure Statement
No competing financial interests exist.
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. The contents of this publication do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States government. The authors assume full responsibility for the accuracy and completeness of the ideas presented.