Total joint arthroplasty (TJA), is one of the most successful operations in modern
medicine; however, it remains an expensive procedure in an era of constrained health care
resources. Arthritis affects 49.9 million Americans with 21.1 million experiencing
arthritis-attributable activity limitations. As these numbers are expected to increase
significantly by 2030, the demand for primary total knee arthroplasties (TKA) by 673% to
3.48 million procedures/year. Periprosthetic joint infection (PJI), with its disastrous
implications, continues to challenge the orthopaedic community. Practicing orthopaedic
surgeons continue to invest efforts to minimize surgical site infection (SSI). Kamath et
al. evaluated characteristics and resource utilization associated with revision
arthroplasty for PJI using the Nationwide Inpatient Sample. The authors found that PJI
was the most common indication for revision total knee arthroplasty (TKA), and the third
most common reason for revision total hip arthroplasty (THA). Prophylactic antibiotics
aim to provide protection against bacteria most likely to gain access to the surgical
site during the procedure and in the perioperative period. The two most common bacteria
causing contamination and subsequent deep infection in TKA are Staphylococcus aureus and
coagulase-negative staphylococci.
While antibiotic regimens for antimicrobial prophylaxis might carry different risks and
side-effect profiles, e.g., hypersensitivity reactions (including anaphylaxis), acute
kidney injury, and Clostridium difficile infection, there are a number of studies which
validate the importance of the preoperative dose of antibiotics in decreasing
periprosthetic joint infection (PJI) and surgical site infection (SSI) in total joint
arthroplasty (TJA). However, there are conflicting recommendations/guidelines as to the
optimal timing and the optimal duration perioperative antibiotics. The American Academy
of Orthopaedic Surgeons (AAOS), the Centers for Disease Control (CDC), and SCIP
guidelines recommend that prophylactic antibiotics be completely infused within one hour
before the surgical incision. The US advisory statement recommends that antimicrobial
prophylaxis be administered within one hour before incision and discontinued within 24
hours after the end of the operation, while European guidelines recommend a single dose
within 30 minutes before incision.
Recently, the Center for Disease Control (CDC) published its updated guidelines for
prevention of SSI prevention that included a recommendation regarding peri-operative
antibiotic prophylaxis. Based on their evaluation of the available literature, the CDC
recommended that a single dose of peri-operative antibiotics be utilized for patients
undergoing clean-contaminated surgical interventions, advocating for no prophylaxis after
the incision is closed in the operating room. This guideline encompasses several
surgeries where implants are utilized, including arthroplasty, spine fusion, and fracture
fixation. Furthermore, it was classified as a category IA-strong recommendation with high
quality evidence. However, much of the literature cited for this recommendation is based
on cardiothoracic, vascular, and general surgeries, where few or no implants are
utilized. It is important to recognize that these surgical cohort may behave differently
from the orthopaedic patient population in terms of infection risk and severity of
infection outcomes.
This clinical research protocol seeks to address the lack of knowledge and Level I data
around the optimal antimicrobial prophylaxis and to address the question if a single
preoperative dose is enough compared to additional postoperative prophylaxis. Several
smaller clinical studies have used pre- and post-intervention periods to assess the
effect of antibiotic duration for surgical prophylaxis. Tang et al launched a surgical
wound infection surveillance program to monitor all orthopaedic surgeries and changed the
prophylactic antibiotic regimen from intravenous cefuroxime (one preoperative and 2
postoperative doses every 8 hours) to one single preoperative dose of intravenous
cefazolin for all clean orthopaedic surgeries. The authors of this study found no
significant difference in the superficial and deep wound infection rates in 1,367 primary
arthroplasties performed with a single preoperative dose of cefazolin versus 3 doses of
cefuroxime. The deep wound infection rate for THA was 1.1% (95% CI, 0%-3.3%) in the
cefuroxime group and 1.1% (95% CI, 0%-2.2%) in the cefazolin group (p=1.0). The deep
wound infection rate of TKA was 1.6% (95% CI, 0%-3.8%) in the cefuroxime group and 1.0%
(95% CI, 0.3%-1.7%) in the cefazolin group (p=0.63).121 In a retrospective review of
1,341 TJAs, Williams and Gustilo found no difference in deep infection rates between a 3
day and 1 day course of prophylactic antibiotics, but emphasized the importance of the
preoperative dose, which was 2g of cefazolin. Mauerhan compared the efficacy of a one-day
regimen of cefuroxime with a 3-day regimen of cefazolin in a prospective, double-blinded,
multicenter study of 1,354 patients treated with arthroplasty and concluded that there
was no significant difference in the prevalence of wound infections between the two
groups.[34] In the group treated with primary THA, the prevalence of deep wound infection
was 0.5% (1/187) for those treated with cefuroxime compared with 1.2% (2/168) for those
who had received cefazolin. In the group treated with a primary TKA, the rate of deep
wound infection was 0.6% (1/178) for those treated with cefuroxime compared with 1.4%
(3/207) for those who had received cefazolin. Heydemann and Nelson, in a study of hip and
knee arthroplasty procedures, initially compared a 24-hour regimen of either nafcillin or
cefazolin with a 7-day regimen of the same and found no difference in the prevalence of
infection. They then compared a single preoperative dose with a 48-hour regimen and again
found no difference in infection prevalence. A total of 466 procedures was performed
during the 4-year study. No deep infections developed in either the one-dose or 48-hour
antibiotic protocol group. A deep infection developed in one (0.8%) of the 127 patients
in the 24-hour protocol group and in two (1.6%) of the 128 patients in the 7-day protocol
group for an overall infection rate of 0.6% (3/466). The authors recognized that as a
result of the small sample sizes, the study lacked the power to compare the one dose and
the more than one dose categories. In two trials, a total of 1609 patients were randomly
assigned to receive 1.5 g of cefuroxime intravenously every 8 hours for a total of 16
hours (n = 1511) or 24 hours (n = 98) postoperatively versus 1600 patients given no
postoperative prophylaxis. Both studies showed no difference between treatment groups
suggesting that current available evidence may not support the efficacy of postoperative
antibiotic prophylaxis for the prevention of surgical-site infections.
Antibiotics have been a critical public health tool since the discovery of penicillin in
1928, saving the lives of millions of people around the world. Today, however, the
emergence of drug resistance in bacteria is reversing the miracles of the past eighty
years, with drug choices for the treatment of many bacterial infections becoming
increasingly limited, expensive, and, in some cases, nonexistent. The Centers for Disease
Control and Prevention (CDC) estimates that drug-resistant bacteria cause two million
illnesses and approximately 23,000 deaths each year in the United States alone. The
Centers for Disease Control and Prevention (CDC) estimates that drug-resistant bacteria
cause two million illnesses and approximately 23,000 deaths each year in the United
States alone (https://www.cdc.gov/drugresistance/). The National Action Plan for
Combating Antibiotic-resistant Bacteria provides a roadmap to guide the Nation in rising
to this challenge. Developed in response to Executive Order 13676: Combating
Antibiotic-Resistant Bacteria - issued by President Barack Obama on September 18, 2014 -
the National Action Plan outlines steps for implementing the National Strategy for
Combating Antibiotic-Resistant Bacteria and addressing the policy recommendations with
regard to antibiotic stewardship as outlined by the President's Council of Advisors on
Science and Technology (PCAST). One of the goals of the National Action Plan is the
implementation of evidence-based infection control practices can prevent the spread of
resistant pathogens and questions the way surgeons use prophylactic antibiotics in the
preoperative period.
The scientific rationale for antibiotic prophylaxis is to inhibit or eliminate
contaminating microorganisms that gain access to the surgical site during the procedure.
Thus, the goal of administering preoperative antibiotics is to allow for adequate tissue
(blood, soft tissue, and bone) concentrations by the time of incision. Thus, these
antibiotics should exceed the minimum inhibitory concentration (MIC) for the organisms
most likely to be encountered for the duration of the operation. While the role of
perioperative antibiotic prophylaxis is well established, controversy exists about best
clinical practice guidelines with regard to antibiotic regimen and route of
administration. The results of the proposed study will be used to establish a clinical
practice guidelines for antimicrobial prophylaxis in elective total joint arthroplasty.