Preoperative strategies to prevent periprosthetic joint infection after knee replacement: evidence-based recommendations for multidisciplinary practice

1) Introduction

Knee replacement is one of the most performed surgical procedures, with its incidence projected to increase in the coming years.^1–3 While knee replacement substantially improves the quality of life for patients with osteoarthritis, it may involve complications. Despite continuous advancements in surgical techniques and perioperative management, periprosthetic joint infection (PJI) remains the most prevalent cause of implant failure.⁴ The occurrence of PJI is estimated to be between 1% and 2% in primary knee arthroplasty, with rates rising to approximately 10% in revision procedures.^5,6

The development of periprosthetic joint infection (PJI) is influenced by a combination of patient-related factors and conditions, and surgical considerations.^7–10 Preventive strategies are crucial to minimizing the risk of PJI and improving patient outcomes; they require a multidisciplinary approach, integrating patient optimization, vigilant postoperative care, and aseptic surgical procedures.^11–16 Preventive strategies are categorized into preoperative, perioperative, and postoperative measures, with preoperative optimization playing a critical role in reducing infection risk.^17–35 Addressing modifiable risk factors before surgery, such as diabetes control, nutritional status, bacterial decolonization, and lifestyle modifications, has been shown to significantly lower the likelihood of PJI.^20–28 Additionally, a thorough preoperative evaluation, including risk stratification, patient education, and multidisciplinary collaboration, is essential for optimizing surgical outcomes.

This review aims to translate current scientific evidence into practical, evidence-based recommendations for physicians, orthopaedic surgeons, and multidisciplinary teams to enhance preoperative patient management and implement effective strategies to minimize the risk of periprosthetic joint infection (PJI) in individuals undergoing knee arthroplasty.

2) Methodology

This review was conducted to evaluate preoperative strategies aimed at reducing the risk of periprosthetic joint infection (PJI) in patients undergoing knee replacement.

Literature Search Strategy

A comprehensive literature search was performed using PubMed/Medline to identify relevant studies addressing preoperative strategies for PJI prevention in knee replacement. The search terms included “knee arthroplasty,” “knee replacement,” “periprosthetic joint infection,” “prevention,” and “preoperative.” The search encompassed articles published in English between January 2000 and December 2024.

Eligibility Criteria

Studies were selected based on the following inclusion and exclusion criteria:

• Inclusion Criteria:

  • Review articles, observational studies, and randomized controlled trials (RCTs) relevant to preoperative prevention of PJI.

  • Studies focusing on modifiable patient-related risk factors, preoperative optimization strategies, and infection control measures.

  • Guidelines and consensus statements from recognized orthopaedic and infection control societies.

• Exclusion Criteria:

  • Studies focusing solely on perioperative or postoperative infection prevention.

  • Case reports, expert opinions without supporting data, and articles not published in English.

Data Extraction and Analysis

Relevant works were critically analysed based on study design, sample size, methodology, and relevance to preoperative PJI prevention. Key findings were synthesized to provide evidence-based recommendations for clinical practice, emphasizing practical applications for healthcare professionals managing patients undergoing knee replacement.

Due to heterogeneity in study design, outcome reporting, and populations, no formal meta-analysis was conducted. Results were grouped according to the type of preoperative risk factors evaluated (e.g., comorbidity control, dietary nutrition and lifestyle modification, bacterial decolonization, local knee control, etc.).

3) Results

Prevention strategies can be categorized into preoperative, perioperative (including intraoperative), and postoperative measures.²³ The preoperative factors to be addressed before knee replacement surgery are summarized in Table 1.

Preoperative factors contribute to the development of the disease through both systemic and localized mechanisms.^23–30 Several preoperative factors should be optimized to minimize the risk of periprosthetic joint infection (PJI) and improve surgical outcomes in knee arthroplasty (TKA). These factors can be categorized into general and local considerations:

1. General Factors

   • Metabolic and Comorbidity Management

     • Diabetes Control: Maintain optimal glycaemic levels (HbA1c <7%) to reduce infection risk.

     • Anaemia Correction: Optimize haemoglobin levels preoperatively to minimize transfusion-related risks.

     • Obesity and Malnutrition: Encourage weight reduction in patients with a body mass index (BMI) >40 kg/m2 and address protein or vitamin deficiencies (e.g., vitamin D, albumin).

   • Bacterial Decolonization

     • Staphylococcus aureus Screening: Mupirocin nasal decolonization and chlorhexidine washes can reduce bacterial load.

     • Oral and Dental Hygiene: Treat active infections and ensure good oral health before surgery.

     • Urinary Tract Screening: Identify and treat asymptomatic bacteriuria in high-risk patients.

   • Lifestyle Modifications

     • Smoking Cessation: Recommended at least four weeks before surgery to improve wound healing.

     • Alcohol Reduction: Excessive alcohol use should be managed to enhance immune function and recovery.

   • Prehabilitation and Functional Optimization

     • Physical Activity and Sarcopenia Management: Strengthening programmes to improve muscle function and postoperative rehabilitation.

     • Mental Health Considerations: Address psychiatric conditions that may affect adherence to postoperative care.

2. Local Factors

   • Knee Joint Condition

     • Avoid Intra-Articular Injections: Corticosteroid injections should be avoided for three months before surgery due to the increased infection risk.

     • Evaluation of Prior Surgeries: Assess residual implants, prior infections, or unresolved joint issues that could influence surgical outcomes.

     • Skin Integrity: Identify and manage skin conditions (e.g., ulcers, dermatitis) to reduce bacterial colonization.

   • Patient Education and Compliance

     • Antiseptic Showering Protocols: Encourage chlorhexidine showers before admission.

     • Nutritional Counselling: Educate patients on dietary modifications to support healing.

Addressing these modifiable preoperative factors through a multidisciplinary approach improves surgical success and reduces PJI risk in knee replacement patients.

4) Comorbidity Control

4.1) Metabolic Disorders

Metabolic disorders represent a significant risk factor for periprosthetic joint infection (PJI) following total joint arthroplasty. Poorly controlled comorbidities and abnormal laboratory parameters can substantially elevate the incidence of PJI.^30,31 Key risk factors include diabetes mellitus (DM), anaemia, obesity, hypoalbuminaemia, vitamin D deficiency, liver disease, hypothyroidism, and kidney disease.³² Identifying and addressing these factors preoperatively enables surgeons to optimize patient health and surgical outcomes, thereby reducing the likelihood of PJI.³³

Diabetes mellitus is one of the most widespread chronic diseases globally, with its prevalence increasing over recent decades.²⁹ It is a known contributor to the progression of severe osteoarthritis, resulting in a growing number of diabetic patients undergoing total joint arthroplasty (TJA) each year.^34,35 Poor glycaemic control, particularly elevated HbA1c levels, has been strongly linked to an increased risk of periprosthetic joint infection (PJI).³⁶ Additionally, fructosamine has been suggested as a reliable predictive marker for glycaemic management in these patients.³⁵

Lovecchio et al.³⁷ reported that diabetes adversely impacts clinical outcomes following primary total lower extremity arthroplasty, with diabetic patients facing a significantly higher likelihood of postoperative medical complications and revision surgery within the first month after joint replacement.³⁸

Previous research on the interplay between diabetes and the immune system has demonstrated that prolonged hyperglycaemia impairs leukocyte function, thereby increasing the risk of both superficial and deep tissue infections in the perioperative period.^39–43 Additionally, diabetes has been shown to have detrimental effects on the musculoskeletal system, leading to delayed collagen synthesis, impaired wound healing, and reduced phagocytic activity. These factors collectively heighten the risk of infection and contribute to slower postoperative recovery.⁴⁰

Given these risks, stringent aseptic protocols and appropriate antibiotic prophylaxis are crucial for patients with diabetes during the perioperative period. Agos⁴¹ reported that effective glycaemic control during surgery significantly reduced infection rates in patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA). To mitigate these risks, preoperative optimization of blood glucose levels is recommended, particularly for patients with haemoglobin A1c levels between 8% and 9% or glucose levels ranging from 180 to 200 mg/dL. Achieving optimal diabetes management before undergoing TJA may require several months or more of dedicated treatment and monitoring.⁴²

Anaemia is a common condition among patients undergoing total joint arthroplasty (TJA) and has been associated with an increased risk of periprosthetic joint infection (PJI). The incidence of PJI is reported to be higher in anaemic patients (4.3%) compared to non-anaemic individuals (2%). Preoperative anaemia, defined as a haemoglobin level below 13.0 g/dL in men and 12.0 g/dL in women, is recognized as an independent risk factor for surgical site infection (SSI) and PJI in TJA patients. Low haemoglobin levels not only elevate the risk of perioperative allogenic blood transfusions, but also contribute to a higher likelihood of postoperative PJI.

Preoperative anaemia is prevalent among orthopaedic patients,^44,45 with an estimated 21% to 35% of individuals undergoing elective orthopaedic procedures being affected.⁴⁴ Studies have demonstrated a strong correlation between preoperative anaemia and increased transfusion rates, higher infection risks, prolonged hospital stays, greater postoperative complications, and elevated mortality rates in orthopaedic patients. Additionally, lower haemoglobin (Hb) levels before surgery have been linked to extended hospitalization, higher mortality, and a heightened risk of readmission, particularly in patients with hip fractures.^45,46

Patients undergoing total joint replacement frequently receive preoperative anaemia management through patient blood management (PBM) programmes. PBM strategies encompass perioperative iron supplementation, antifibrinolytic therapy, aggressive hydration, and regional anaesthesia, as well as restrictive transfusion protocols, minimally invasive surgical techniques, anatomically guided incisions, and the use of a bipolar sealer to minimize blood loss.⁴⁷ Although autologous blood transfusion presents certain disadvantages, iron supplementation, alone or in combination with erythropoietin, has been shown to be a safe and effective approach for optimizing haemoglobin levels in patients undergoing TJA.⁴⁸ Furthermore, multiple studies have established a strong correlation between preoperative anaemia and an increased risk of infection in the TJA population.^45,49

In addition to anaemia, several comorbidities have been identified as independent risk factors for periprosthetic joint infection (PJI). These include coagulopathy, congestive heart failure, chronic pulmonary disease, depression, renal disease, peripheral vascular disease, and valvular disease, in addition to pulmonary circulation disorders, psychoses, and metastatic tumours.^31–36

4.2) Inflammatory and Rheumatic Diseases

Patients with inflammatory joint diseases are at an increased risk of developing periprosthetic joint infections (PJI) following total joint arthroplasty.^50–54 For example, rheumatoid arthritis (RA) has been strongly associated with a higher incidence of surgical wound infections and prosthetic implant complications.⁵³ Individuals with RA have a 1.6 times greater risk of developing PJI compared to those undergoing joint replacement for osteoarthritis, primarily due to a compromised inflammatory response.⁵⁰

The precise etiopathogenetic mechanism underlying this increased infection risk remains unclear. Some studies suggest that iatrogenic immunosuppression from long-term disease-modifying treatments significantly contributes to infectious complications. Others propose that the elevated risk is intrinsic to the disease itself, as chronic immune activation in inflammatory conditions may impair normal immune defences.^54,55

Additionally, persistent systemic inflammation, especially in rheumatoid arthritis, negatively affects wound healing, increasing vulnerability to bacterial colonization at the surgical site.⁵⁵ This combination of immune dysregulation and delayed tissue repair further elevates the likelihood of PJI in patients with rheumatic and inflammatory diseases. Moreover, patients with rheumatoid arthritis frequently experience malnutrition, which further predisposes them to infection-related risk factors.^50–53

Immunosuppressive therapies, including corticosteroids and disease-modifying antirheumatic drugs (DMARDs) such as methotrexate, have also been implicated in increasing infection susceptibility. According to the International Consensus Meeting on PJI, DMARD therapy should be temporarily discontinued before surgery, with the timing based on the specific drug’s half-life. Methotrexate, which inhibits tumour necrosis factor (TNF) and interleukin-6 (IL-6), has been shown to elevate infection risk, further complicating postoperative recovery in these patients.⁵¹

5) Dietary, Nutrition, and Lifestyle Modifications

5.1) Obesity

Many candidates for joint replacement suffer from pain and symptoms of osteoarthrosis because they are overweight or obese with a severe reduction of daily activity and sport activity, or complete immobilization.^56–58 Extremely obese patients are considerably more at risk of PJI and have a four times higher infection incidence than thinner patients. The risk of infection has been found to increase with body mass index (BMI).⁵⁹ In obese patients with BMI >40 kg/m2 the risk of infection rises by 3.3 times, while in morbidly obese individuals with a BMI >50 kg/m2, the risk of PJI grows by 21 times.³¹

Obesity is also associated with other comorbidities such as diabetes mellitus and cardiovascular disease. Furthermore, obese patients require extra time for technical considerations during surgical procedures, due to the need for blood transfusions and the presence of additional medical disorders that affect the duration of anaesthesia.^60,61 Patients who have a BMI of 35 or higher and present other risks for PJI,⁶² as well as those who have a BMI of 40 or more, should postpone surgery and optimize their conditions by receiving nutritional and bariatric surgery consultations.^7,63–65

5.2) Dietary, Nutrition, and Lifestyle Modifications in Preoperative Optimization

The preoperative optimization of diet, nutrition, hydration, and lifestyle factors plays a crucial role in reducing the risk of periprosthetic joint infection (PJI) and improving surgical outcomes in total joint replacement. Addressing these modifiable risk factors enhances immune function, promotes wound healing, and reduces perioperative complications.

Malnutrition is associated with several adverse outcomes, including prolonged hospital stays, impaired wound healing and PJI.¹⁸ One of the key risk factors is inadequate protein levels, as indicated by serum albumin and total protein concentrations.⁶⁶

Malnutrition is a medical condition characterized by insufficient protein intake, resulting in increased patient frailty. It is commonly defined by laboratory markers such as serum albumin levels below 3.5 g/dL, serum transferrin levels under 200 mg/dL, and serum prealbumin levels below 15 mg/dL.

Moreover, hypovitaminosis plays a significant role in musculoskeletal infections, particularly in the progression of septic conditions. The importance of vitamin D in immune function and infection control has been well documented by multiple authors.^60,66 Therefore, preoperative optimization of serum vitamin D levels should be considered as part of the strategy to reduce the risk of postoperative complications.

Hydration also plays an important role in the prevention of PJI by influencing physiological functions such as immune response and tissue perfusion. Adequate hydration improves renal function and the elimination of toxins, contributing to a healthier environment for surgical recovery. Therefore, optimal hydration practices should be integrated into preoperative care to improve patients’ conditions.^22,53

5.3) Sarcopenia and the Role of Physical Activity in Preoperative Optimization

Sarcopenia is a widespread condition characterized by progressive muscle loss and reduced strength in older adults, leading to increased morbidity, mortality, and adverse healthcare outcomes.⁶⁷ Following total knee arthroplasty (TKA), sarcopenia has been linked to a higher risk of complications,⁶⁸ including periprosthetic joint infection (PJI).⁶⁹

The sarcopenic obesity phenotype, defined by increased body fat and decreased muscle mass, is associated with higher infection rates, in addition to impaired functional recovery and prolonged rehabilitation after joint replacement. Furthermore, extended periods of inactivity before and after surgery can contribute to weight gain, which negatively impacts cardiovascular health and metabolic function⁶⁹; however, in a systematic review and meta-analysis on the impact of sarcopenia in patients undergoing total joint arthroplasty, Sumbal⁷⁰ found no association between sarcopenia and PJI.

Sarcopenia may contribute to poorer postoperative outcomes in total knee replacement patients. Ardeljan⁶⁸ reported an increase in implant-related complications within two years, although research specifically linking sarcopenia to PJI risk remains limited. Despite this, preoperative sarcopenia screening, including muscle mass assessments, is recommended for patients undergoing TKA.

Effective sarcopenia management primarily involves nonpharmacological interventions, which are beneficial for all affected individuals. These include lifestyle modifications, targeted muscle-strengthening exercises, and physical therapy, complemented by pharmacological treatments when necessary.⁶⁸ Preoperative exercise programmes, focused on muscle strengthening and improving knee range of motion, have been shown to enhance postoperative recovery and minimize complications in TKA patients.

Regular physical activity plays a crucial role in maintaining muscle mass and strength, thereby reducing the risk of sarcopenia while supporting immune function. Additionally, exercise promotes better blood circulation and oxygenation of tissues, which enhances wound healing and lowers infection risk. Improved glycaemic control in physically active individuals also helps minimize diabetes-related infections, further supporting successful TKA outcomes.⁶⁷

6) Bacterial Decolonization

Remote infections, including urinary tract, dental, skin, respiratory, and active musculoskeletal types, can act as sources of haematogenous bacterial spread, significantly increasing the risk of periprosthetic joint infection (PJI). Studies indicate that over 98% of PJI cases are caused by bacterial pathogens, with Staphylococcus aureus and coagulase-negative staphylococci responsible for 50% to 60% of infections.^71,72 Proper identification and management of preoperative infections are essential to minimize the risk of postoperative complications and implant-related infections.

6.1) Nasal Decolonization in Preoperative Infection Prevention

Over the past decade, bacterial decolonization has gained increasing importance in orthopaedic surgery, particularly in industrialized countries, as a critical measure to reduce surgical site infections (SSIs) and periprosthetic joint infection (PJI). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in the nasal cavity is estimated at 2.2%, while Staphylococcus aureus colonization is detected in over 4% of patients. Due to this high colonization rate, preoperative screening for S. aureus has become a widely recognized standard practice among hospital administrators and orthopaedic surgeons.⁷³

Nasal decolonization begins with screening for S. aureus and its variants using a nasal swab as part of the preoperative assessment. The presence or absence of bacterial colonization is determined using either bacterial culture methods or real-time polymerase chain reaction (RT-PCR) analysis. If a patient tests positive for S. aureus, the scheduled arthroplasty procedure is typically postponed, allowing sufficient time for nasal decolonization therapy to be completed before surgery.

It is recommended that patients undergoing joint replacement surgery use mupirocin 1 mg applied twice daily for five consecutive days, combined with daily antiseptic showers as part of a comprehensive infection control protocol. The surgical procedure can be rescheduled within 30 days after completing decolonization therapy to ensure optimal infection prevention.

According to a systematic review and meta-analysis conducted by Sadigursky⁷³ and Zhu,⁷⁴ nasal S. aureus screening and decolonization significantly reduced the risk of SSI, PJI, and superficial infections compared to patients who did not undergo decolonization. However, Baratz⁷⁵ reported that 22% of patients remained colonized with MRSA despite undergoing the decolonization protocol. Interestingly, no significant differences in PJI risk were observed between patients following the protocol and those in the control group, suggesting that additional measures may be required for complete bacterial eradication in some cases.

6.2) Anal Decolonization in Preoperative Infection Prevention

Anal screening, meanwhile, has not been shown to have either a significant protective effect or an increased risk concerning surgical site infections.^6,16 However, it is often associated with hospital-acquired infections and prolonged hospital stays. Due to its direct relationship with the intestinal microbiota, effective decontamination is not feasible. Nevertheless, preoperative intestinal preparation is already recognized as a best practice in surgical protocols.

6.3) The Role of Dental Clearance in Infection Prevention for Arthroplasty

Dental clearance and oral decontamination are now recognized as essential components of infection prevention protocols for both medical and surgical admissions.^76–78 While guidelines strongly recommend preoperative dental evaluation, clinical studies specifically examining its impact on joint replacement outcomes remain limited. There is insufficient evidence to conclusively support the use of antibiotic prophylaxis in preventing surgical site infections (SSIs) in orthopaedic surgery, though some works suggest it may be beneficial.⁷⁶

The available evidence on the role of preoperative dental clearance and hygiene assessment in reducing infection risks for arthroplasty patients is limited, particularly in cases where high-risk factors are present.⁷⁶ However, for orthopaedic surgeons, preoperative dental assessment may be valuable, particularly in patients with a history of oral infections, previous endodontic treatments, or recent tooth extractions, as these conditions could potentially contribute to bacteraemia and increase the risk of periprosthetic joint infection (PJI).⁷⁶

6.4) Other Infections (Urinary Tract, Gastrointestinal, Fungal Infections, Etc.)

Preoperative infection screening should include urinary tract infections (UTIs), as UTIs are widely recognized as moderate- to high-risk factors for periprosthetic joint infection (PJI).^79–90 The urinary tract serves as a common entry point for pathogens, which can reach the surgical site or prosthetic components through haematogenous dissemination or direct contamination.

Several studies have investigated the impact of standard urinary antibiotic prophylaxis in reducing postoperative infections, particularly in patients with significant leukocyturia.^80,81 However, findings remain inconclusive, as while some research suggests a reduction in infection rates, others highlight the potential risks, such as acute kidney injury, which itself is a risk factor for PJI.⁷⁹ Current evidence does not support the routine use of preoperative antibiotic therapy in cases of asymptomatic bacteriuria.^81,82 Instead, it is strongly recommended that symptomatic UTIs be eradicated before surgery and urinary symptoms be closely monitored postoperatively.⁸⁰

Additionally, patients with inflammatory bowel disease (IBD), who often exhibit gut microbiome dysregulation, are at an increased risk of PJI. Although the exact mechanism remains unclear, this association may be linked to bacterial translocation from the inflamed intestinal mucosa or a dysregulated immune response, both of which could facilitate systemic bacterial spread and contribute to prosthetic joint infections.⁸³

6.5) Skin Decolonization

Iannotti⁷ recommends that high-risk patients undergo daily chlorhexidine baths for five days before surgery as part of a comprehensive infection prevention strategy to minimize the risk of postoperative complications. Preoperative skin decolonization with chlorhexidine cleansing has been shown to effectively reduce PJI rates, demonstrating superior antimicrobial efficacy compared to regular soap.⁸⁴

Although fungal periprosthetic joint infections (PJI) are rare, accounting for approximately 1%-2% of all PJI cases, they present greater challenges in both diagnosis and management compared to bacterial infections.⁷¹

Patients with superficial skin or nail mycosis appear to have an elevated risk of bacterial infections following total joint arthroplasty (TJA), although the exact underlying mechanism remains unclear. Some evidence suggests that preoperative fungal infections across multiple body sites may be more indicative of an immune system alteration rather than a direct fungal transmission risk to the surgical site.

In a retrospective comparative study, Lin⁸⁵ reported that 8.6% of patients with preoperative mycosis who underwent total knee replacement developed bacterial PJI, whereas no infections were observed in patients without mycosis. This finding suggests a potential correlation between fungal colonization and increased susceptibility to bacterial infections.

7) Surgical Strategies for Reducing Local Infection Risk

Surgeons should implement preventive measures to minimize local infection risk by avoiding procedures or interventions that could increase the likelihood of periprosthetic joint infection (PJI).

7.1) Intra-Articular Injections and Infection Risk

Preoperative intra-articular injections have been linked to a higher risk of postoperative periprosthetic joint infection (PJI) following total knee arthroplasty (TKA).⁸⁶ The risk appears to be time-sensitive, with a greater likelihood of infection when injections are administered closer to the surgery date.⁸⁷

A systematic review by Richardson⁸⁸ found that hyaluronic acid or corticosteroid injections given within 99 days before TKA significantly increased the risk of developing PJI. However, a systematic review and meta-analysis by Charalambous⁸⁹ reported no significant association between prior steroid injections and the incidence of deep or superficial infections. While the evidence remains conflicting, careful consideration should be given to timing and necessity when administering preoperative intra-articular injections to reduce infection risk.

7.2) Arthroscopy Prior to Knee Replacement

Gu,⁹⁰ in his study on the risk of arthroplasty revision in patients who underwent arthroscopy before total knee replacement, suggested that in individuals with severe osteoarthritis, arthroscopy performed within 36 weeks before knee replacement increases the risk of periprosthetic joint infection (PJI).⁹⁰

7.3) Previous Joint Infection and the Risk of Periprosthetic Joint Infection

Patients with a history of septic arthritis due to prior surgery or intra-articular injections should undergo thorough preoperative evaluation to rule out the presence of quiescent or residual infection before proceeding with total joint arthroplasty (TJA).⁹¹ Proper risk assessment and microbiological screening are essential to minimize the risk of periprosthetic joint infection (PJI) in these high-risk patients.

In a study of 207 total joint replacements, Tan⁹² found no clear consensus on the optimal timing between previous septic arthritis and elective TJA. Portier⁹³ recommended taking intraoperative synovial fluid and tissue samples during arthroplasty and initiating empirical antibiotic therapy until culture results are available to ensure the absence of active infection.

Total joint arthroplasty in patients with prior septic arthritis can be performed using either a single- or two-stage approach. However, in a systematic review and meta-analysis of 413 patients, Luo⁹⁴ found no significant difference in reinfection rates between the two methods, suggesting that both approaches can be considered based on patient-specific factors and surgical planning.

8) Miscellaneous Risk Factors (Smoking, Substance Use, Alcohol, and Psychosis)

The relationship between smoking, substance use, alcohol consumption, and psychiatric disorders with periprosthetic joint infection (PJI) is complex, as these factors can independently and synergistically contribute to higher infection risk, delayed healing, and poor surgical outcomes.^95,96 Smoking and chronic alcohol use impair immune function and wound healing, while substance abuse and psychiatric conditions may lead to poor adherence to postoperative care and hygiene protocols, further increasing the likelihood of complications. Additionally, patients with severe mental illness often experience nutritional deficiencies and reduced access to healthcare, compounding their risk of surgical site infections and delayed recovery. Addressing these modifiable risk factors through preoperative counselling, multidisciplinary support, and cessation programmes is essential to improve postoperative outcomes in total joint arthroplasty patients.^97–108

8.1) Smoking

Smoking and tobacco use are well-established risk factors for periprosthetic joint infection (PJI) and delayed wound healing following total joint arthroplasty (TJA). Smoking suppresses immune function, reducing the body’s ability to combat infections and promote tissue repair.⁹⁷

Nicotine contributes to these risks through multiple mechanisms, including vasoconstriction, which restricts blood flow to tissues, leading to impaired oxygenation, delayed wound healing, and a higher likelihood of surgical site infections. Additionally, chronic systemic inflammation caused by smoking may further predispose patients to postoperative infections.⁹⁸

Several studies suggest that at least four weeks of smoking cessation before elective surgery can significantly reduce the risk of surgical complications, including infection, delayed healing, and implant failure.⁹⁹ Therefore, preoperative smoking cessation programmes should be strongly encouraged as part of comprehensive risk reduction strategies in TJA patients.

8.2) Substance Abuse, HIV, and Periprosthetic Joint Infection Risk

Substance abuse and HIV infection are significant risk factors for periprosthetic joint infection (PJI) due to their impact on immune function and overall health status. Intravenous drug users (IVDU) are particularly susceptible to bloodstream infections, which can lead to haematogenous spread and subsequent PJI.^100,101

Chronic drug use weakens immune defences, making individuals more prone to postoperative infections and delayed wound healing. Additionally, patients with substance use disorders often exhibit poor adherence to post-surgical care protocols, which further increases their risk of complications and implant failure. HIV-positive patients, particularly those with uncontrolled viral loads or low CD4 counts, also face a higher incidence of postoperative infections, emphasizing the need for preoperative optimization and infection control strategies in these high-risk populations.¹⁰¹

8.3) Alcohol Consumption and Its Impact on Periprosthetic Joint Infection

Chronic alcohol consumption is a well-documented risk factor for periprosthetic joint infection (PJI) due to its detrimental effects on immune function, wound healing, and coagulation. Long-term alcohol use can lead to liver disease and coagulopathy, both of which increase susceptibility to infections and impair the body’s ability to respond to surgical stress.

Additionally, alcoholism is strongly associated with malnutrition, particularly protein and vitamin deficiencies, which are essential for tissue repair, immune response, and overall surgical recovery. Patients with alcohol dependency may also exhibit poor adherence to postoperative care instructions, further increasing their risk of complications and implant failure. Given these risks, preoperative screening and counselling for excessive alcohol use should be an integral part of infection prevention strategies in total joint arthroplasty (TJA).

8.4) Psychosis and the Increased Risk of Periprosthetic Joint Infection

Patients with psychotic disorders, such as schizophrenia and bipolar disorder, are at an increased risk of periprosthetic joint infection (PJI) due to several contributing factors. These include poor self-care and hygiene, lower adherence to medical treatments, and impaired pain perception, which may result in delayed recognition and treatment of infection symptoms.^30,101

Additionally, certain antipsychotic medications can negatively impact immune function and wound healing, further elevating the risk of postoperative complications. When psychosis is accompanied by other risk factors, such as smoking, heavy alcohol consumption, or substance abuse, the likelihood of PJI increases exponentially.^102,103

To mitigate these risks, patients with psychotic disorders should undergo comprehensive preoperative screening, with multidisciplinary interventions including substance use treatment, mental health support, and smoking cessation programmes to improve postoperative outcomes and reduce infection risk.¹⁰³

9) Conclusion

Preventing periprosthetic joint infection in knee replacement requires a multidisciplinary, proactive approach that begins well before the surgical procedure. While surgeons play a critical role in intraoperative infection control, many modifiable risk factors can be effectively addressed during the preoperative period, significantly improving patient safety and surgical outcomes.

Simple yet impactful preoperative interventions, such as lifestyle modifications, as well as weight management, metabolic disease optimization, bacterial decolonization, muscle strengthening, and knee mobility enhancement, can substantially reduce PJI risk, shorten hospitalization, and accelerate recovery. Addressing these factors before surgery allows healthcare providers to mitigate preventable complications and improve overall patient resilience.

Patients with one or more risk factors should undergo a structured, multidisciplinary preoperative assessment, integrating patient education in addition to targeted medical treatments and routine follow-ups, to optimize their condition before surgery. Standardized risk factor management protocols, involving surgeons, general practitioners, infectious disease specialists, physiotherapists, and nutritionists, can enhance infection prevention strategies and ultimately improve long-term TKA success rates.

This review serves as a starting point for raising awareness of the importance of a multidisciplinary preoperative approach. By implementing evidence-based, practical interventions, healthcare providers can make joint replacement a safer and more effective procedure, ensuring better patient outcomes and reducing the burden of PJI in orthopaedic surgery.

Author Contributions

Conceptualization, H.Z. and I.A.; methodology, H.Z.; software, M.M.; validation, V.D.G.; resources, H.Z. and M.M.; data curation, R.G.; writing—original draft preparation, I.A, M.M. and R.G.; writing—review and editing, H.Z and V.D.G.; supervision, F.P. All authors have read and agreed to the published version of the manuscript.

Funding and Conflicts of interest statements

There was no funding source for the manuscript. The authors declared no conflict of interest.