Preventing periprosthetic joint infections: how to lower infection rates

As the number of joint replacements being performed around the world grows every year, so do the number of periprosthetic joint infections (PJI). The troublesome rise in antibiotic resistance as well as the antibiotic tolerance of biofilms, presents risk to patients and limited and shrinking treatment options for clinicians. What measures can you and your surgical team take prior to, during, and after joint replacement that will help lower the risk of PJI?

The frequency of joint replacement is forecast to continue its upward trend in all countries. A study in 2019 by Ackerman et al predicted that Australia could expect total knee (TKR) and hip (THR) replacements to increase by 276% and 208%, respectively, by 2030 [1]. Whether or not joint replacement growth estimates take into account a country’s changing demographics, body mass index (BMI), and gender factors [2], it is agreed that joint arthroplasty will only become more common [3–5]. As the number of implantations and cumulative number of joints in place increases, so too will the number of reported complications, including related infections [6, 7].

Economic burden of infection

Despite the evolution and adoption of more stringent infection control protocols, infection is a very serious problem throughout the world’s hospitals. It carries both a psychological and economic burden for both patients and their families, the health care team, as well as the health care system. With a wider consideration of costs to society, health care-associated infection costs in the US have been estimated to exceed $200 billion annually [8].

Periprosthetic joint infection (PJI) is a complication that is both “serious and complex” [9]. As orthopedic surgeons, you will have had patients that were impacted by PJI, with some cases responding to treatment more readily than others [10]. Treating PJI can increase procedure costs by up to 24 times compared with cases without PJI [12]. The longer treatment takes and the more surgical intervention that is required (such as two-stage revisions), the higher the costs [6, 12, 13].

Antimicrobial resistance

However, the persistence of infection encountered in some patients, despite antibiotic treatment, highlights a global problem that has been brewing since antibiotics came into use. Antimicrobial resistance is developing to the antibiotics and fungicides that even 50 years ago were effective and rapid treatments. Methicillin-resistant Staphylococcus aureus (MRSA) is estimated to cause at least 20,000 annual in-hospital deaths in the US alone [11].

Biofilms: a complex, persistent neighborhood

However, PJI’s are difficult to treat because pathogen microorganisms colonize the prosthesis, growing in biofilms [12]. Biofilms are “structurally complex” which gives them the emergent property of an evolved protection against the body’s immune response as well as against antibiotics, and even physical debridement [13]. A biofilm is more persistent than its parts as it is structured in a layered matrix—a community that alters its metabolic function and even communicates with itself via quorum sensing [14, 15].

How does bacteria form a biofilm?

A short animation from the Centre for Microbial Innovation, at the University of Auckland, New Zealand, illustrates the process. Created by Andrew Dopheide.

Ciofu et al point out that biofilm-associated antimicrobial tolerance is “fundamentally different from antimicrobial resistance” and attribute this to the following multi-factorial causes [16]:

• Antimicrobial tolerance increases with biofilm age (maturation)
• Biofilm matrices restrict antimicrobial penetration
• Bacterial metabolic activity varies within the layers of biofilm
• Specific gene expression unique to biofilms can provide enhanced tolerance
• Persister cells divide slowly or not at all, inhibiting antibiotic pathways
• The in vivo environment may have low oxygen tension, limiting the effectiveness of antibiotics dependent on the presence of oxygen for uptake, such as fluoroquinolones, beta‐lactams, and aminoglycosides

It has been observed that biofilm-associated infections are diversifying and the impact of this may be underestimated [17]. The persistent characteristics of biofilm and the role it plays in PJI highlights the importance of correct use of biofilm active antibiotics in implant-associated infections.

 
Some have even gone so far as to suggest that if a patient’s risk factors (body mass index higher than 40kg/m2, diabetes mellitus on insulin therapy, kidney and liver disease, and vascular disease of the lower extremities) cannot be controlled or eliminated a significant time before the initial arthroplasty, the operation should be cancelled as the risk of infection is too great [46].

Trampuz reaffirmed this: “Importantly, if steroids or hyaluronic acid were previously injected in the joint, the prosthesis implantation should be postponed for at least 3 months, better 6 months after last intraarticular injection, to avoid the increased risk of PJI. Similarly, patients with any chronic skin diseases (eg, eczema, psoriasis, chronic skin ulcers), and/or infections in the oral cavity (dental abscess), should be evaluated and treated before elective arthroplasty.”

Let’s take a closer look at a few of the modifiable factors under a surgeon’s control. The following considerations were put forward as potential guidelines by the International Consensus Meeting (ICM) of orthopedic surgeons, held in 2013 and 2018, which aimed to use evidence-based, consensus decision-making to identify best practices for prevention of PJI [47, 48].

 

Nasal screening

Staphylococcus aureus (S. aureus) is a common cause of infection, especially in persons already colonized by these bacteria. A US-based study on the profile of potential high-risk MRSA nasal carriers determined that men, with previous health care exposure, born in the US, over age 60, and with diabetes were of higher risk, while in women, only poverty was found to be the correlating risk factor for being a carrier [49]. The ICM guidelines specify treating known carriers with Mupirocin, but not universally screening [48]. In contrast to this approach, other studies reinforce the use of treat-all strategies [50]. Pelfort et al were able to eliminate TKA surgical site infections from S. aureus by using mupirocin nasal ointment and chlorhexidine soap in their known carrier study population [51].

 

Skin preparation

A study conducted at a surgical ICU quaternary academic medical center in New York found that compared to daily soap and water washing, bathing every other day with 2% chlorhexidine gluconate (CHG) (alternating with soap and water washing) decreased the risk of acquiring infections by 44.5% [52]. Also, preparation of the surgical site with an alcohol-based containing agent has been recommended for reducing infection in ankle arthroplasty [53]. One study even found that if TKA patients used a chlorhexidine gluconate wipe protocol preadmission it reduced infection rates [54]. The ICM recommend washing with CHG at least the night before surgery, and if CHG is unavailable, using antibacterial soap [48]. In Europe, other antiseptics are used for whole-body decolonization, namely octenidin and polihexanid.

 

Immunosuppressive therapy

The ICM guidelines note that in patients with rheumatoid arthritis or other inflammatory diseases who are receiving disease-modifying antirheumatic drugs (DMARDs), these treatments should be stopped prior to joint replacement at an interval based on the drug’s half-life, and therefore each case should be evaluated individually and in tandem with the patient’s rheumatologist [48].

 

Glycemic control

In a 2018 systemic review and meta-analysis of 17 previously published studies, Shohat et al reported that although there was no consensus on an optimal HbA1C threshold, “inadequate” glycemic control raised the risk of PJI [55]. The ICM suggests keeping blood glucose level < 200 mg/dL, including during surgery [48]. However, while the ICM suggests HbA1C < 7% [48], Shohat et al draw attention to their finding that this threshold was not supported by their pooled data and studies are needed to determine new markers for glycemic control [55].

 

New device coatings to battle microorganisms

A 2004 study suggested that up to 50% of implants may be contaminated before they are even implanted [56]. Scientists approaching the problem of PJI from this design angle are developing innovative coatings and surface modifications, and investigating materials with intrinsic antibacterial properties in the hopes of developing a successful product to reduce PJI [57]. Different aspects of bacterial behavior are being targeted but surface modification strategies are of high interest as an implant’s material properties are not altered (see box on dragonfly wings).

Intraoperative infection prevention strategies

Prophylactic antibiotics

The use of prophylactic antibiotics has been shown to reduce the risk of PJI. Keeping the bacteria count low just before, during, and after a surgery greatly decreases the risk of developing an infection as their multiplication is hindered [42]. The World Health Organization (WHO), Society for Healthcare Epidemiology and America (SHEA), the Center for Disease Control (CDC), and the National Institute for Health and Care Excellence (NICE) as well as other groups have all issued various guidelines around antibiotic administration to prevent surgical site infection. Table 2 summarizes a few of the ICM recommendations, which took the above-mentioned groups’ guidelines under consideration when being developed [47].

According to a recently published study, potentially 6,098 PJIs could be prevented in one year and 11,905 within ten years in a cohort of 1,000,000 primary total knee arthroplasty (TKA) and THA patients simply by using cefazolin antibiotics perioperatively during primary arthroplasties. The researchers encourage preoperative allergy testing to help boost cefazolin usage [59].

It is important to note that in most cases, the benefits of prophylactic antibiotics are limited to the first 24 hours after surgery, and if continued further, are not associated with any additional reduction of surgical site infection. In fact, acute kidney injury and Clostridium difficile infection are more likely [60].

 
Table 2. Summary of International Consensus Meeting (ICM) antimicrobial recommendations to prevent PJI

Trampuz emphasizes the need for optimizing perioperative antibiotic prophylaxis. This applies to the timing of prophylaxis, choice, and dose of antibiotic. He recommends that “the antibiotic should be started 30–60 minutes before skin incision and the infusion should be completed before a tourniquet is applied (if used).” He also advises dosing by patient weight and consideration of blood loss.

“The antibiotic of first choice is cefazolin or cefuroxime, which can be administered also in penicillin-allergic patients, except in the case of anaphylaxis (Quincke angioedema or anaphylactic shock). In this case vancomycin or – exceptionally – clindamycin should be given. Both, vancomycin and clindamycin are less evaluated and probably less effective than cephalosporins. The antibiotic dose should be adapted to the body weight and renal function. For example, 2 g of cefazolin is dosed intravenously in patients weighing < 90 kg, 3 g (ie, 50% more) in patients weighing 90−120 kg, and 4 g (ie, 100% more) in patients weighing > 120 kg. The dose should be repeated only if the surgery lasts longer than 3 hours or if more than 2 L of blood is lost. Additional dosing does not improve the prevention but increases the risk of adverse events and development of resistance.”

A guideline will only serve its purpose if it is followed. In the case of prophylactic antibiotic guidelines, noncompliance was documented in 38.7% of 1019 hip and knee arthroplasty patients in a retrospective observational study conducted in Australia. In those with noncompliant dosing, the infection rate was 5.0% but only 1.7% for patients who received compliant dosing [35]. Two aspects of prophylactic antibiotic guidelines that seem to be the most neglected are redosing during long procedures (> 4 hours) and adjusting dosing for patients weighing over 80 kg [35, 61].

 

Reducing operating room traffic

The amount of traffic in the operating room (OR), as determined by the number of door openings, has been indicated as a risk factor for PJI; one study showed that the circulating nurse and surgical implant representatives were the people most frequently in and out of an OR [62]. Airborne bacteria in the OR are most likely introduced by the humans in the room. A single person will shed around 10 million particles/day, and 5–10% of these carry bacteria [63]. Air filtration within the hospital environment results in fewer airborne bacteria.

 

Dressed for success

After examining gown contamination before, during, and after lower limb joint replacement surgery, Qoreishi et al concluded that contamination rates were “concerning”: gowns were found to be contaminated even before surgery even started [64]. One simple change that could be adopted to reduce contamination introduced from the glove-gown interface is simply donning gloves before sleeves are put on. When this approach was tested by residents, through to attending physicians, zero contamination was recorded [65].

In Table 3 below, you can review a multitude of intraoperative infection risk factors, sorted by their known effectiveness in impacting PJI rates.

 
Table 3. Intraoperative factors associated with PJIs

A (clean) tool for the job?

Surgical power tools, such as the drills and saws essential to orthopedics, have complex designs and easily become contaminated during use. Their complex designs make it difficult to fully remove biological matter. Lopes et al looked at contamination of complex surgical tools by biological soils and biofilm after 20 cycles of contamination and reprocessing. They reported that current designs prevent thorough cleaning, for example, noting that the depth gauge accumulated biofilm in its lumen despite being disassembled for cleaning [66].

While the literature rarely contains reports of infection directly linked to power tools, this is probably not indicative of their role as a source of infection. This void in understanding is most likely due to “incomplete reporting, failure to investigate power tools, or lack of surveillance”, say Deshpande et al [67].

 
Postoperative infection prevention strategies

The US Center for Disease Control (CDC) reports that on any given day one of 31 hospital patients will have a hospital-acquired infection [68]. Data has shown that over time, a decrease in the average length of hospital stay for THA patients correlates to lower postoperative complication rates [69].
 

Prophylactic antibiotics for certain procedures

Once a patient has an artificial joint, it is thought that any infection they contract in their body could result in a PJI through hematogenous seeding of the pathogen [70]. A study in 2019 elaborated on the origins of hematogenous PJI, reporting that in 15% of all identified foci a previous intervention or manipulation was documented [32].

This risk is why some doctors prescribe, and patients may ask their doctors about, prophylactic antibiotics before undergoing dental, cardiac, urologic, or gastrointestinal procedures [71]. The American Board of Family Medicine concluded that:

“the literature suggests recommending prophylactic antibiotics only for patients with total joint replacement in the event that they are undergoing a major urologic procedure…or undergoing a routine urologic or dental procedure with 1 or more of the following risk factors: immunocompromise, previous joint infections, malnourishment, hemophilia, HIV, diabetes, malignancy, or a joint implanted within the past 2 years. Patients undergoing routine cardiac procedure should receive any antibiotics routinely given for the procedure but do not need additional antibiotic prophylaxis; those undergoing gastrointestinal procedures do not require prophylactic antibiotics.” [71]

 

Blood transfusion

If joint replacement patients receive allogenic blood transfusions, studies have shown that they are at a higher risk of surgical site infection [72, 73]. While the most effective measures to address this risk are unresolved, according to the ICM [48], reducing operating time and other strategies such as tourniquet use aim to reduce the need for transfusion [74]. Additionally, there are many different ways for orthopedic surgeons to estimate blood loss, varying degrees of accuracy [75]. Gibon et al recommend using Mercuriali’s formula and converting volumes of blood to milliliters (mL) [75].

 

Wound care

In relation to PJI, the ICM calls wound management issues non-emergencies [48], but also indicates that preoperative optimization of patients is critical to lower the risk of wound-related complications. This includes “correction of anemia, the control of hypogycaemia and reversal of anticoagulation agents.” The longer a wound takes to heal, [formation of] a hematoma, and persistent wound drainage all raise the risk of a PJI [18]. The use of Aquacel™ surgical dressing, compared to gauze bandages, has been correlated to a reduced incidence of PJI [76, 77].

Prolonged wound discharge longer than 7 days after surgery is suggestive of early postoperative infection. Trampuz points out that “other, non-infectious reasons for wound healing disturbance must be considered, such as coagulation disorders, malnutrition (hypoproteinemia), or anasarca. If unclear, a low threshold for early revision with change of mobile parts and collection of deep periprosthetic tissue samples is indicated, followed by empiric antibiotic therapy. Mobile parts can be sent for sonication, if available.”

 

Timeline for prevention

There are many strategies that surgeons can employ before, during, and after a joint replacement surgery to lower the risk of a patient contracting an infection. Preventing PJI before it happens is an important component. Figure 1 below summarizes the options and indicates where these fall on a timeline.

 
Conclusion

As Borens reminds us, there is a large degree of responsibility on the whole health care team working together; efforts must be made to include everyone in developing and implementing solutions.

“The more rules you have to apply, and the more people have to change their behavior the more difficult it gets. For example, it has been shown that the traffic in the OR (number of openings of the door) has a direct impact on the infection risk. It is difficult to teach the anesthetists not to wander between the operating theaters. Ideally, one should sit together with the different teams of the OR and look at a checklist of ideal behavior and then compare this to what is actually happening on a day-to-day basis. Then one should make a list of possible improvements and decide as a team on the new rules which will have to be strictly followed by all—from the chief of surgery through to anesthetist to intern to scrub nurse!”

Trampuz agrees with Borens and reaffirms the need for heightened understanding. “Increased awareness of the risk of infection can dramatically reduce the infection rate. It is estimated that about 2/3 of infections can be prevented by good planning and communication. The preventive measures apply also to the environment during surgery, including proper preoperative skin disinfection with an alcohol-based solution, a short operating time, atraumatic surgical technique, limited personnel traffic in the OR, and reducing the amount and volume of talking. All these measures reduce the bacterial burden in the OR air with subsequent risk of microbial colonization of the implant,” concludes Trampuz.

Prevention aside, if a patient does develop an acute or chronic PJI how do you diagnose and treat it? Prompt diagnosis and management are also critical aspects of preventing the progression of infection [63].

Part 2 of this article series looks at diagnostic tools and an algorithm to determine if a joint is infected as well as the most effective ways to figure out what kind of bacteria are present. Part 3 takes you through appropriate treatment options for several PJI scenarios.