ICJR REWIND: Antibiotics for Perioperative Prophylaxis in TJA Patients
The authors review what’s known – and unknown – about issues with the use of antibiotics to prevent surgical site infections in patients undergoing total hip and total knee arthroplasty, including current standards, recent recommendations, and dental prophylaxis, in an article originally published on July 17, 2018.
Andrew M. Pepper, MD; Lewis Moss, MD; and Jonathan M. Vigdorchik, MD
Prevention of surgical site infection (SSI) – specifically, prevention of periprosthetic joint infection (PJI) – has been a topic of intense interest in the medical and surgical community for the last 2 decades. The reasons for this are numerous, but the most intense focus is on preventing the devastating medical, surgical, and economic consequences of PJI, which is generally regarded as a “preventable” complication in patients undergoing elective total joint arthroplasty.
The purpose of this article is to discuss:
- The history of current standards for perioperative antibiotic therapy for prevention of SSI
- The recent recommendations from the Centers for Disease Control and Prevention (CDC)
- The available literature on the timing and selection of antibiotics
- The common issue of prophylactic antibiotics for arthroplasty patients undergoing other invasive medical procedures
The history of the current Surgical Care Improvement Project (SCIP) Guidelines reaches back to 1970 when the CDC began collecting aggregate national data to monitor nosocomial infections in the US. Data from this project, the National Nosocomial Infections Surveillance (NNIS) System, showed that SSIs contributed to one third of all reported nosocomial infections, with 77% of deaths related to infection associated with an SSI.  The data also revealed that only 56% of patients received antibiotics on time and only 41% had antibiotics discontinued within 24 hours postoperatively. [2,3]
The CDC and the Centers for Medicare & Medicaid Services (CMS) developed the Surgical Infection Prevention (SIP) project in 2002 in response to widespread poor adherence to practices proven to decrease the rate of SSIs, with the goal of creating national standardized processes to increase compliance with these practices.  Implementation of the SIP project proved effective in decreasing the rate of postoperative infections nationwide. 
The SCIP Guidelines, first published in 2006, contain specific recommendations of measures to decrease the incidence of postoperative SSIs. These guidelines were compiled by CMS and the Joint Commission with the distinct aim of standardizing quality measures nationally and unifying documentation to allow for long-term reporting and study of outcomes after its implementation. .
The SCIP guidelines contain 7 perioperative, evidence-based measures aimed at decreasing SSIs: 
- Prophylactic antibiotic received within 60 minutes before the first surgical incision
- Prophylactic antibiotic selection for surgical patients
- Prophylactic antibiotics discontinued within 24 hours after surgery
- Cardiac surgery patients with a controlled postoperative blood glucose by 6:00 am the next day
- Surgery patients with appropriate hair removal
- Urinary catheter removed on postoperative day 1
- Surgery patients with perioperative temperature management
The guidelines – along with the Joint Commission announcement that they consider SSI to be a “never event” – have increased national focus on postoperative infection and its effect on morbidity/mortality, as well as incentivized adherence.  The initial goal of the SCIP guidelines was to achieve 25% reduction in SSIs nationwide by 2010. Although adherence to the guidelines was met, there is mixed literature regarding the effect of adherence on postoperative infection rates nationally. [3,7]
The 2013 report from the International Consensus Meeting on Periprosthetic Infections agreed with the SCIP recommendations of a single antibiotic dose perioperatively and postoperative antibiotics for less than 24 hours.  Multiple organizations – Prevention of Periprosthetic Joint infection, the American Academy of Orthopedic Surgeons (AAOS), the CDC, and the International Consensus Group – have endorsed administration of antibiotics within 60 minutes of surgical incision . There is consensus in the recommendations from the National Surgical Infection Prevention Project for discontinuing perioperative antibiotics within 24 hours in non-infected arthroplasty cases. 
PJI rates have precipitously decreased in the last 2 decades to the current rates of 0.30% for total hip arthroplasty (THA) and 1.1% for total knee arthroplasty (TKA), supporting the use of antibiotics preoperatively and no more than 24 hours after surgery. 
2017 CDC Guidelines Review
In 2017, the CDC published new guideline recommendations based on systematic review of the best available evidence on preventing SSIs.  The relevant recommendations for total joint arthroplasty patients from this review include the following:
- Administer preoperative antimicrobial agents only when indicated based on published clinical practice guidelines and timed such that a bactericidal concentration of the agents is established in the serum and tissues when the incision is made (Category IB–strong recommendation; accepted practice).
- No further refinement of timing can be made for preoperative antimicrobial agents based on clinical outcomes (no recommendation/unresolved issue).
- The literature search did not identify randomized controlled trials that evaluated the benefits and harms of weight-adjusted parenteral antimicrobial prophylaxis dosing and its effect on the risk of SSI.
- The literature search did not identify sufficient randomized controlled trial evidence to evaluate the benefits and harms of intraoperative re-dosing of parenteral prophylactic antimicrobial agents for the prevention of SSI.
- In clean and clean-contaminated procedures, do not administer additional prophylactic antimicrobial agent doses after the surgical incision is closed in the operating room, even in the presence of a drain (Category IA–strong recommendation; high-quality evidence).
- Randomized controlled trial evidence suggests uncertain trade-offs between the benefits and harms regarding intraoperative antimicrobial irrigation (eg, intra-abdominal, deep, or subcutaneous tissues) for the prevention of SSI.
- The literature search did not identify randomized controlled trials that evaluated soaking prosthetic devices in antimicrobial solutions before implantation for the prevention of SSI.
- Do not apply antimicrobial agents (i.e., ointments, solutions, or powders) to the surgical incision for the prevention of SSI (Category IB–strong recommendation; low-quality evidence). Application of autologous platelet-rich plasma is not necessary for the prevention of SSI. Consider the use of triclosan-coated sutures for the prevention of SSI. Randomized controlled trial evidence suggests uncertain tradeoffs between the benefits and harms regarding antimicrobial dressings applied to surgical incisions after primary closure in the operating room for the prevention of SSI.
- Implement perioperative glycemic control and use blood glucose target levels less than 200 mg/dL in patients with and without diabetes (Category IA–strong recommendation; high to moderate–quality evidence). The literature search did not identify randomized controlled trials that evaluated lower (<200mg/dL) or narrower blood glucose target levels than recommended in the guideline, nor the optimal timing, duration, or delivery method of perioperative glycemic control for the prevention of SSI. In addition, the literature search did not identify randomized controlled trials that evaluated the optimal hemoglobin A1C target levels for the prevention of SSI in patients with and without diabetes.
- Maintain perioperative normothermia (Category IA–strong recommendation; high to moderate–quality evidence). The literature search did not identify randomized controlled trials that evaluated strategies to achieve and maintain normothermia, the lower limit of normothermia, or the optimal timing and duration of normothermia for the prevention of SSI.
- For patients with normal pulmonary function undergoing general anesthesia with endotracheal intubation, administer increased FIO2 during surgery and after extubation in the immediate postoperative period. To optimize tissue oxygen delivery, maintain perioperative normothermia and adequate volume replacement (Category IA–strong recommendation; moderate-quality evidence).
- Advise patients to shower or bathe (full body) with soap (antimicrobial or non-antimicrobial) or an antiseptic agent on at least the night before the operative day (Category IB–strong recommendation; accepted practice).
- Perform intraoperative skin preparation with an alcohol-based antiseptic agent unless contraindicated (Category IA–strong recommendation; high-quality evidence). Application of a microbial sealant immediately after intraoperative skin preparation is not necessary for the prevention of SSI. The use of plastic adhesive drapes with or without antimicrobial properties is not necessary for the prevention of SSI. Consider intraoperative irrigation of deep or subcutaneous tissues with aqueous iodophor solution for the prevention of SSI.
These guidelines were developed with the assistance of clinical experts and with direction from the CDC’s Healthcare Infection Control Practices Advisory Committee (HICPAC).  After initial draft of the recommendations, a period of public review and comment was allowed. The author group and HICPAC reviewed public input and updated the guidelines with new literature. The final draft was voted on by the CDC/HICPAC, with publication in May 2017.
Orthopedic surgeons and national leadership participated in the public review of the proposed guidelines. The AAOS was outspoken regarding the implications of these guidelines for orthopedic patients.  They identified potential conflicts of interest for some of the authors and also questioned the inclusion of 14 guidelines in the final recommendations that were not identified in the initial review of literature. They questioned the possibility that evidence was unintentionally overlooked. 
The AAOS also took a hard stance against the CDC’s strong recommendation that prophylactic antibiotics not be administered postoperatively. They note that this recommendation was based on systematic review of evidence from heterogeneous surgical subspecialties and patient populations and that generalizing the information to orthopedics – and, specifically, arthroplasty patients – was not advisable due to the potential for substantial negative impact on these patients.  The AAOS requested that the guidelines grant latitude in this recommendation to allow orthopedic surgeons to consider postoperative prophylactic antibiotics for patients who have an implant utilized in their surgical care, as per their recommendations based on the orthopedic literature. [11,14-17] Despite these concerns, the CDC guidelines were published without change to the recommendation on postoperative prophylactic antibiotic administration.
The American Association of Hip and Knee Surgeons (AAHKS) published a position statement on the new CDC guidelines in November 2017. AAHKS echoed the concerns expressed by AAOS regarding postoperative antibiotic administration, stating that the CDC recommendation, “contradicts current international standards of care with limited evidence and study” and it is based on heterogeneous evidence (type of surgical procedure, antibiotic regimen, and antibiotics used). The AAHKS position statement noted that much of the included orthopedic evidence is older studies with historically high rates of PJI that do not reflect the current lower rate of PJI achieved by standard perioperative prophylactic antibiotic usage, including antibiotic use for less than 24 hours postoperatively. 
The AAHKS position statement also expressed concern that the included evidence appears underpowered to accurately discern the safety of withholding postoperative prophylactic antibiotics, citing a lack of Level I evidence to guide such a recommendation.  AAHKS said that the Foundation for Arthroplasty Research and Education (FARE) has taken a proactive approach to answering this question with a funded grant to Thorsten M. Seyler, MD, PhD, of Duke University, for a prospective randomized controlled trial intended to elucidate the effect of single prophylactic antibiotic dosing versus 24-hour antibiotic dosing in TKA. 
Tailored versus Universal Prophylactic Antibiotics
Surprisingly, the question of which antibiotics are appropriate for prophylaxis in total joint arthroplasty patients remains unanswered. It has been well documented that gram-positive organisms such as Staphylococcus species cause most PJIs. [19, 20] Antibiotic-resistant organisms, including methicillin-resistant Staphylococcus aureus, are responsible for an increasing number of PJIs. Despite this, all accepted guidelines recommend universal antibiotic selection. [1,21-26] Whether universal antibiotic regimens or tailored regimens are more efficacious remains controversial.
Tan et al  evaluated whether a universal antibiotic regimen or a regimen tailored to the patient’s comorbid conditions affected PJI rates and infecting organisms. Although their study identified that certain comorbid conditions affect which organism causes a PJI, there was no significant difference in the rate of PJI for patients receiving standard prophylaxis versus vancomycin to cover resistant Staphylococcal strains. They concluded that a universal prophylactic antibiotic protocol is appropriate in the prevention of PJI. 
Bosco et al  were interested in the increasing number of gram-negative organisms contributing to PJI. They, therefore, studied the effects of expanded gram-negative prophylactic coverage on prevention of PJI, demonstrating that its utilization decreased the rate of PJI overall in THA. They also found that tailoring prophylactic antibiotics to the emergence of evolving pathogens is safe and effective. 
Overall, universal prophylaxis protocols appear safe and effective in preventing PJI, but as pathogens evolve, we should be cautious to monitor for emerging microbial trends in PJI.
Current Dental Prophylaxis Recommendations
Historically, it had been believed that invasive procedures, such as dental cleaning or colonoscopy, after total joint arthroplasty carried of risk of acute hematogenous PJI from the resulting bacteremia. [29, 30] Orthopedic surgeons, therefore, recommended that patients receive prophylactic antibiotics prior to invasive procedures to decrease this theoretical risk.  Recently, this practice has been called into question, and there continues to be great disparity in utilization of this practice.
Slover et al  studied the cost associated with the use of prophylactic antibiotics prior to invasive dental procedures and found that the practice is likely not cost-effective in low-risk patients. They concluded that little quality evidence is available to guide decision making, indicating that surgeons should weigh the benefits of antibiotic use against the possible adverse effects of the drugs. 
The AAOS has attempted to fill the gap by developing an Appropriate Use Criteria (AUC) document to guide orthopedic surgeons and dentists. [32, 33]. The AUC is “designed to help determine the appropriateness of treatments of the heterogeneous patient population routinely seen in practice. The best available scientific evidence is synthesized with collective expert opinion on topics for which randomized clinical trials are not available or are inadequately detailed for identifying distinct patient types.” [32, 33].
The AUC includes a web-based decision-making tool that includes variables such as:
- The invasiveness of the proposed dental procedure
- The immune status of the patient
- The presence of diabetes and the level of glucose control
- The history of prior PJI
- The time since the index total joint arthroplasty
By considering these variables, the surgeon and dentist can determine whether antibiotic prophylaxis is appropriate, and if so, which antibiotic would be best for a given patient.
Although there is still limited strong evidence to make distinct conclusions, the AUC represents the best available attempt to summarize available evidence and expert opinion to avoid PJI while limiting needless antibiotic cost and adverse effects of antibiotic use.
Andrew M. Pepper, MD, and Lewis (Kip) Moss, MD, are adult reconstruction fellows, Insall Scott Kelly Institute, Department of Orthopedic Surgery, NYU Langone Orthopedic Hospital, New York, New York. Jonathan M. Vigdorchik, MD, is an Assistant Professor of Orthopedic Surgery, Associate Fellowship Director in Adult Reconstruction, and Co-Director of Robotics in Orthopedic Surgery at NYU Langone Orthopedic Hospital, New York, New York.
The authors have no disclosures relevant to this article.
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