University of Groningen
Early prosthetic joint infection after primary total joint arthroplasty
Löwik, Claudia Aline Maria
DOI:
10.33612/diss.97641504
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Publication date: 2019
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Citation for published version (APA):
Löwik, C. A. M. (2019). Early prosthetic joint infection after primary total joint arthroplasty: risk factors and treatment strategies. Rijksuniversiteit Groningen. https://doi.org/10.33612/diss.97641504
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General introduction and
outline of this thesis
1
Background
Osteoarthritis (OA) is the most common joint disorder worldwide.1 It can
develop in any type of joint, although weight-bearing joints, such as the hip and knee, are most commonly affected. OA is recognized as a substantial source of disability, since it causes considerable pain and reduced mobility.2
Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are highly successful surgical treatment modalities for advanced OA of the hip and knee. In 2017, 29,937 primary THAs and 26,030 primary TKAs were performed in the Netherlands3 and over a million THAs and TKAs are performed annually in the
USA.4 Due to general ageing of the population and increasing levels of obesity,
the incidence of OA continues to rise. Because of this increasing incidence and changing thresholds for arthroplasty surgery, the demand for THA and TKA continues to rise too and is expected to keep rising in the coming decades.5
Although most patients experience good results after THA and TKA, some patients develop postoperative complications. One of the most serious complications after joint arthroplasty and an important cause for revision arthroplasty is prosthetic joint infection (PJI), developing in approximately 1-2% of primary arthroplasties and up to 10% of revision arthroplasties.6,7
Although this percentage is relatively low, the absolute number of patients with PJI is substantial, given the large and still-increasing number of patients who undergo total joint arthroplasty surgery. Prevention of PJI is therefore an important issue, especially given the significant burden it poses on patients and society: PJI is associated with high morbidity and mortality, as well as high socioeconomic costs due to prolonged hospital stay, additional surgical procedures and antimicrobial treatment.8
Classification of PJI
PJI can develop at any time point after surgery. Several classification systems for PJI have been composed over the years.9-14 Most systems divide PJI into early,
late and hematogenous PJI, depending on the time from joint arthroplasty to development of PJI and duration of symptoms. A large proportion of PJIs occur within the first three months after implantation and are defined as early PJIs.15,16
Early PJIs are typically acquired at the time of surgery through intraoperative contamination and are caused by relatively virulent microorganisms, such as
Chapter 1
have an acute presentation with a warm, swollen, painful, erythematous joint, often with features of sepsis. Late PJIs can also present acutely but usually have more subtle signs, such as chronic pain, a sinus tract with chronic drainage and sometimes prosthetic loosening at the bone-cement interface. Late PJIs present more than three months after index surgery. Just as early PJIs, they are also typically acquired at the time of index surgery but are caused by less virulent or indolent microorganisms, such as coagulase negative staphylococci. Some patients develop hematogenous PJI, in which the prosthetic joint gets infected after a longstanding infection-free period. These infections are typically secondary to an infection at a different site in the body, such as dental infections. Patients with hematogenous PJI usually present with the same acute symptoms as patients with early PJI.
Risk factors for PJI
Minimizing the risk of PJI after THA and TKA requires elimination of two types of risk factors: 1) factors that increase the risk of exposure of the hip or knee joint to microorganisms, and 2) factors that limit a patient’s ability to eliminate intra-articular microorganisms. One of the most important type-1 risk factors is prolonged wound leakage,17,18 a difficult complication as it could be a symptom
of an already existing PJI as well as a risk factor for developing PJI. Moreover, surgical wounds may show prolonged wound leakage for reasons other than infection (such as hematoma, seroma or fatty necrosis) and take longer to heal without development of an infection. As leaking wounds increase the risk of exposure to microorganisms by providing a porte d’entrée, prolonged wound leakage should be considered as potentially imminent PJI.19 Identified type-2 risk
factors include obesity, diabetes mellitus, immunodeficiency and rheumatoid arthritis.20,21 Literature indicates that the risk of PJI increases exponentially with
body mass index.20,22 Patients with an oncological condition requiring tumor
resection are often immunodeficient due to their need for chemotherapy or radiotherapy.23,24 Further, patients with rheumatoid arthritis are at increased
risk due to their immunosuppressive therapy and susceptibility to infectious disorders of bone, joint and soft tissue.25 The number of comorbidities also
limits a patient’s ability to eliminate intra-articular microorganisms, thus increasing the risk of PJI.26
1
Treatment strategies for PJI
There are several surgical and non-surgical treatment strategies for PJI, such as debridement, antibiotics and implant retention (DAIR), revision surgery and suppressive antibiotic therapy. The aim of performing a DAIR is to reduce the infective load of intra-articular microorganisms, provide extensive debridement and start antibiotic therapy in order to retain the prosthesis and avoid more invasive surgery (such as revision arthroplasty). During DAIR the pre-existing wound is opened and the joint cavity is debrided and thoroughly lavaged. If possible, modular components are exchanged. Multiple deep-tissue biopsies are subsequently obtained for culturing, broad-spectrum intravenous antibiotic treatment is started, and the wound is meticulously closed. DAIR is the recommended treatment for patients with early PJI, and is most successful for early acute PJI, in which symptoms exist for less than three weeks.27,28
The higher effectiveness of DAIR in early acute PJI compared with late PJI is due to biofilm formation, a highly complex process in which microorganisms attach to a surface and proliferate into a mature biofilm (Figure 1). Nearly all microorganisms are capable of forming a biofilm, although some types of microorganisms are more potent than others. In vitro studies showed that a biofilm already starts to form within hours of inoculation of bacteria,29 but
these experiments are performed under optimal circumstances for bacterial growth and do not include the complexity of the host’s environment and the protective effect of its immune system.30 Recent in vivo models showed that
a biofilm is evident after two weeks, but extends and is covered by fibrinous tissue and multiple host cells after six weeks.31 The process of biofilm formation
does vary widely between bacterial species, size of inoculum and hosts.32,33
Due to multiple phenotypic and genotypic changes in the process of biofilm formation, embedded microorganisms become unresponsive to almost any antibiotic treatment once a mature biofilm is formed.35,36 As a consequence, a
PJI cannot be cured with DAIR without removal of the implant. In that case a different surgical treatment option for PJI is revision arthroplasty, which involves replacing the primary prosthesis with a new prosthesis. The prosthesis, including the mature biofilm, is removed, achieving infection control in approximately 90% of patients.37,38 However, benefits of DAIR over revision arthroplasty include
retention of the prosthesis, preservation of bone stock, shorter duration of the surgical procedure, decreased risk of intraoperative fractures (caused by removal of components and implantation of cement spacers) and faster postoperative rehabilitation.39,40 And yet, rates of infection control after DAIR vary widely from
Chapter 1
37% to 88%.41-44 This variation in infection control after DAIR stresses the need
for careful selection of eligible patients, especially since performing a DAIR procedure could reduce the effectiveness of subsequent revision surgery.45-48
Moreover, this indicates that surgical techniques of a DAIR procedure should be optimized to improve infection control after DAIR.
Aims and outline of this thesis
The studies described in this thesis aim to examine and evaluate the risk factors and treatment strategies for early PJI. The first part of the thesis focuses on patient groups at risk for PJI, such as obese patients, oncology patients and patients with prolonged wound leakage after THA and TKA. The second part of this thesis strives to provide insights on factors that can influence the treatment success of DAIR, such as patient selection, use of local antibiotics during DAIR and optimization of the timing of DAIR.
Part 1: Evaluation of patients at risk for early PJI
Chapter 2 presents a review of the available literature on the diagnosis and
treatment of prolonged wound leakage after THA and TKA. As patients
Figure 1. Description of various stages involved in the development of a biofilm. 1) Bacterial adhesion to the surface, 2) cell-to-cell adhesion, 3) attached cell monolayer, 4) maturation of a biofilm and formation of exopolymeric substance, and 5) detachment. Image credit: D. Davis34
1
with prolonged wound leakage are at increased risk for developing PJI, it is important to optimally diagnose and treat these patients. Remarkably, there are no evidence-based guidelines on this topic that can guide orthopaedic surgeons in their decision-making process. The lack of scientific consensus motivated this review of the available literature.
Chapter 3 provides a review of the available literature on PJI in orthopaedic
oncology patients. PJI rates among these patients are high due to local and systemic immunodeficiency caused by chemotherapy or radiotherapy. Moreover, these patients usually require large implants because of the need for extensive tumor resections. Even though this patient category is clearly different than regular patients receiving THA or TKA, literature on oncologic PJI is scarce. Hence information on regular PJI is usually applied to oncology patients too. To outline the topics that need future research, conducted specifically on oncology patients, this review describes the current evidence on the definition, diagnosis and treatment of oncologic PJI.
Obese patients are another well-known patient category with an increased risk of PJI. Chapter 4 describes the clinical and microbiological characteristics of obese patients with early PJI, aiming to identify characteristics that contribute to this increased risk and to ultimately improve preventive measures for this specific patient category.
Part 2: Improving treatment strategies for early PJI
Chapter 5 shows the results of the external validation of a preoperative risk
score for DAIR failure. As success rates of DAIR vary widely, it is important to select the right patients for this procedure: rates of infection control by DAIR could be optimized and the number of more extensive revision surgeries reduced. To estimate the risk of DAIR failure prior to surgery, thereby selecting the right patients for DAIR, Tornero et al. developed the KLIC score.49 This score
preoperatively calculates the risk of DAIR failure by evaluating five patient-related factors: 1) chronic renal failure (Kidney), 2) Liver cirrhosis, 3) Index surgery, 4) Cemented prosthesis and 5) CRP >115 mg/L (KLIC). Before the KLIC score can be implemented as a standard tool in clinical practice, it has to be validated in an external cohort.
In addition to selecting the right patients for DAIR, infection control after DAIR can also be improved by optimizing surgical techniques and antibiotic treatment. Chapter 6 provides results on the efficacy of
gentamicin-Chapter 1
impregnated beads and sponges in patients with early PJI treated with DAIR. In the Netherlands, gentamicin-impregnated beads and sponges are routinely applied to achieve higher rates of infection control. However, the beneficial effects of applying these local antibiotic carriers have never been demonstrated.
Moreover, it is important to perform DAIR at the right time point. To this end, Chapter 7 describes the rate of infection control after DAIR according to the interval between index surgery and DAIR. As the success rate of DAIR is dependent on the time needed for bacteria to form a mature biofilm at the surface of the prosthesis, PJI can no longer be cured by DAIR once embedded bacteria in the biofilm become unresponsive to antibiotic treatment. So far, the time interval until formation of this mature biofilm is unknown. Hence it cannot be estimated whether it is useful to perform a DAIR procedure at a certain time point after joint arthroplasty.
While Chapter 7 describes the optimal timing of DAIR in patients with early PJI in general, Chapters 8 and 9 focus on the optimal timing of DAIR in patients with prolonged wound leakage after THA and TKA. As there are no evidence-based guidelines on the best treatment for prolonged wound leakage, the Dutch orthopaedic community stated in 2015 that this topic constitutes an important knowledge gap. To address this gap, Consortium Orthopaedic Research (CORE) assembled the LEakage After primary Knee and hip arthroplasty (LEAK) study group. Chapter 8 provides the results of a survey the LEAK study group conducted among Dutch orthopaedic surgeons on the definition, diagnosis and treatment of prolonged wound leakage, to assess current clinical practice in the Netherlands.
Based on the results of this survey and the literature review in Chapter 2, the LEAK study group designed the LEAK study, which is described in Chapter 9. This nationwide multicenter randomized controlled trial compares the revision rates, clinical effectiveness and cost effectiveness of DAIR and non-surgical treatment. It is hypothesized that performing DAIR at an early time point is helpful in preventing and treating PJI and salvaging the implant in patients with prolonged wound leakage after THA and TKA.
Chapter 10 presents a general discussion on the main findings of the studies
described in this thesis. It also provides future perspectives and implications for clinical practice.
1
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