Total hip and knee arthroplasty are among the most successful reconstructive procedures in modern orthopaedic practice, providing substantial improvements in pain, mobility, and quality of life for patients with end-stage joint disease. With increasing life expectancy, obesity, osteoarthritis prevalence, and access to surgical care, the global volume of TJA continues to rise. Periprosthetic joint infection remains one of the most challenging complications of arthroplasty. Although contemporary infection rates after primary TJA are generally low, PJI is associated with revision procedures, prolonged antimicrobial therapy, functional deterioration, psychological distress, healthcare expenditure, and increased mortality. A large Canadian population-based study of 100,674 primary THAs reported a cumulative PJI incidence of 1.44% at 15 years, while a corresponding study of 129,613 primary TKAs reported a cumulative incidence of 1.65% at 15 years. Most infections occurred within the first several postoperative years.1-3 PJI is biologically complex. Infection may arise from perioperative inoculation, early postoperative wound contamination, contiguous spread, or later hematogenous seeding. Host susceptibility influences the ability of inoculated microorganisms to establish biofilm on prosthetic surfaces. Consequently, infection risk is determined not only by microbial exposure but also by metabolic health, immune function, tissue perfusion, nutrition, wound healing, surgical duration, blood loss, and previous infection history. Earlier systematic reviews consistently identified obesity, diabetes, rheumatoid arthritis, tobacco use, steroid therapy, previous surgery, prolonged operative time, and malnutrition as important determinants, although the strength of evidence differs substantially between factors.4-7 The 2019 American Academy of Orthopaedic Surgeons guideline considered obesity the patient-related factor supported by moderate-strength evidence, while numerous additional comorbidities were supported by limited or conflicting evidence.1 More recent studies have expanded the evidence base to include nutritional biomarkers, operative duration, MRSA colonization, asymptomatic bacteriuria, prior cellulitis, and interactions between multiple risk factors. This review therefore aimed to provide an updated systematic synthesis of risk factors for PJI following primary THA and TKA, distinguish modifiable from non-modifiable factors, and identify clinically actionable targets for perioperative optimization.

2.1 Study Design This systematic review was structured according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 principles.8 The review focused on risk factors for PJI following primary THA or TKA. The review question was: Among adults undergoing primary total hip or total knee arthroplasty, which patient-related, disease-related, infectious, behavioral, nutritional, or perioperative factors are associated with an increased risk of subsequent PJI? 2.2 Information Sources The search strategy covered PubMed/MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library from database inception to 31 January 2026. Reference lists of relevant systematic reviews, meta-analyses, clinical guidelines, and eligible primary studies were additionally screened. A total of 2,874 records were identified through database searching and reference-list screening, comprising 1,046 records from PubMed/MEDLINE, 842 from Embase, 506 from Scopus, 388 from Web of Science, 64 from the Cochrane Library, and 28 from reference-list searching. Before screening, 612 duplicate records and 94 records removed for other reasons were excluded, leaving 2,168 records for title and abstract screening Of these, 1,924 records were excluded during title and abstract screening, and 244 reports were sought for retrieval. Twenty-eight reports could not be retrieved, leaving 216 full-text reports for eligibility assessment. Following full-text evaluation, 195 reports were excluded: review, editorial, or other non-original articles (n = 52); studies without a primary THA/TKA population (n = 41); studies that did not evaluate PJI risk factors (n = 36); studies with inadequate outcome data (n = 28); duplicate or overlapping cohorts (n = 23); and non-English publications or reports for which the full text was unavailable (n = 15). Consequently, 21 studies fulfilled the eligibility criteria and were included in the systematic review. The complete study-selection process is presented in Figure 1. 2.3 Search Strategy A core search strategy was: ("periprosthetic joint infection" OR "prosthetic joint infection" OR PJI OR "deep infection") AND ("total joint arthroplasty" OR "total hip arthroplasty" OR THA OR "total knee arthroplasty" OR TKA) AND ("risk factor" OR predictor OR obesity OR diabetes OR smoking OR malnutrition OR hypoalbuminemia OR anemia OR rheumatoid arthritis OR immunosuppression OR steroid OR urinary infection OR bacteriuria OR MRSA OR operative time OR transfusion OR previous surgery). Search terms were adapted to the syntax of each database. 2.4 Eligibility Criteria • Adults undergoing primary THA or TKA were included. • The study evaluated subsequent deep surgical-site infection or PJI. • One or more potential risk factors were assessed. • Cohort, case-control, registry, systematic-review, or meta-analytic methodology was used. • Adjusted or unadjusted measures of association, or sufficient descriptive data, were reported. Studies were excluded when they focused exclusively on treatment failure after established PJI, shoulder or elbow arthroplasty, superficial infection without PJI outcomes, non-human models, or isolated case reports. 2.5 Data Extraction The following information was extracted: author, publication year, study design, arthroplasty type, sample size, follow-up period, PJI definition, investigated risk factors, adjusted or pooled effect estimates, and principal conclusions. Risk factors were categorized as demographic factors; obesity and metabolic factors; nutritional and hematological factors; inflammatory and immunological disorders; infectious and colonization-related factors; behavioral factors; and surgical and perioperative factors. 2.6 Quality Assessment Primary observational studies were interpreted using domains consistent with ROBINS-I, including confounding, participant selection, exposure measurement, outcome ascertainment, missing data, and selective reporting. Systematic reviews and meta-analyses were assessed according to search comprehensiveness, study selection, risk-of-bias assessment, heterogeneity, and consistency of reported findings. 2.7 Data Synthesis A narrative systematic synthesis was undertaken. Published pooled ORs, RRs, and hazard ratios (HRs) were retained in their original form. A new universal pooled estimate was not calculated because the risk factors represented different exposures and because several meta-analyses contained overlapping primary populations.

3.1 Characteristics of the Evidence Base The literature included large national and regional arthroplasty registries, institutional cohorts, case-control studies, and several systematic reviews and meta-analyses. Sample sizes ranged from several hundred arthroplasties to population-based datasets exceeding 100,000 procedures. The most extensively investigated factors were obesity, diabetes, smoking, male sex, rheumatoid arthritis, ASA status, malnutrition/hypoalbuminemia, anemia, previous surgery, transfusion, and operative duration. Table 1. Major studies contributing to the evidence on PJI risk after total joint arthroplasty. Author, year Design / population Arthroplasty Major factor(s) evaluated Main finding Pulido et al., 20089 Prospective institutional cohort; 9,245 patients THA/TKA ASA, obesity, transfusion, UTI, hospitalization PJI incidence 0.7%; higher ASA, morbid obesity, transfusion and longer hospitalization increased risk Bongartz et al., 200810 Cohort; 657 arthroplasties in RA THA/TKA Rheumatoid arthritis, revision, prior PJI RA associated with increased infection; prior PJI and revision further increased risk Malinzak et al., 200911 Retrospective cohort; 8,494 arthroplasties THA/TKA Obesity, diabetes, age Morbid obesity and diabetes associated with increased deep infection Jamsen et al., 200912 Finnish registry; 43,149 knee arthroplasties TKA Sex, RA, previous fracture, revision Male sex, seropositive RA and previous fracture increased infection risk Bozic et al., 201213 Medicare cohort; 83,011 patients TKA Multiple medical comorbidities CHF, pulmonary disease, anemia, diabetes, depression, renal disease and obesity predicted PJI Jamsen et al., 201214 Cohort; 7,181 arthroplasties THA/TKA Obesity, diabetes, hyperglycemia Morbid obesity OR 6.4; diabetes OR 2.3 Bozic et al., 201215 Medicare cohort THA Medical comorbidities Multiple chronic medical conditions associated with increased PJI risk Namba et al., 201316 Registry; 56,216 TKAs TKA BMI, diabetes, sex, ASA, operative time BMI >=35, diabetes, male sex and ASA >=3 increased infection risk Zhu et al., 20154 Systematic review/meta-analysis THA/TKA Multiple factors BMI, diabetes, steroids, hypoalbuminemia, RA, transfusion, prolonged surgery and previous surgery associated with PJI Kunutsor et al., 20165 Systematic review/meta-analysis; 512,508 patients THA/TKA Patient-related risk factors Male sex, smoking, obesity, diabetes, RA, depression, steroids and previous surgery increased risk Kong et al., 20176 Meta-analysis THA/TKA Patient, comorbidity and surgical factors Male sex, obesity, ASA >2, diabetes, RA, UTI and longer surgery associated with PJI Bohl et al., 201617 NSQIP cohort; 49,603 patients THA/TKA Hypoalbuminemia Low albumin associated with SSI and adverse postoperative outcomes Bedard et al., 201918 Systematic review/meta-analysis; 14 studies THA/TKA Tobacco Tobacco users had increased PJI risk; current smokers had greater risk than former smokers Ren et al., 202119 Meta-analysis Primary THA/TKA Patient-related factors High BMI, diabetes, RA and several comorbidities associated with PJI McMaster Arthroplasty Collaborative, 202020 Population cohort; 100,674 THAs THA Sex, diabetes, discharge status Male sex HR 1.43; diabetes HR 1.51 McMaster Arthroplasty Collaborative, 202221 Population cohort; 129,613 TKAs TKA Long-term predictors 15-year cumulative PJI incidence 1.65% Shin et al., 202422 Meta-analysis; 427,361 TKAs TKA Operative duration >90 min OR 1.50; >120 min OR 1.56 Carender et al., 202423 Cohort; 21,550 THAs THA BMI and cumulative risk factors Severe obesity had progressively greater relative and absolute PJI risk Ghaseminejad-Raeini et al., 202424 Meta-analysis; 42,592 patients THA/TKA Asymptomatic bacteriuria ASB associated with increased pooled PJI odds, but organisms generally differed Erling et al., 202625 National database; 105,926 TKAs TKA Previous cellulitis Prior cellulitis associated with increased 2-year PJI risk Javidmehr et al., 202626 Systematic review/meta-analysis THA/TKA MRSA colonization Residual PJI risk remained higher among MRSA-colonized patients despite decolonization Abbreviations: ASA, American Society of Anesthesiologists; BMI, body mass index; PJI, periprosthetic joint infection; RA, rheumatoid arthritis; THA, total hip arthroplasty; TKA, total knee arthroplasty; UTI, urinary tract infection. 3.2 Obesity Obesity was the most consistently supported modifiable patient-related risk factor. The systematic review by Kunutsor et al. reported pooled RRs of 1.60 for BMI >=30 kg/m2, 1.53 for BMI >=35 kg/m2, and 3.68 for BMI >=40 kg/m2 compared with lower BMI categories.5 A dose-response relationship is also apparent in primary studies. Jamsen et al. reported an infection rate increasing from 0.37% among normal-BMI patients to 4.66% among the morbidly obese, with an adjusted OR of 6.4.14 Recent long-term data emphasize the importance of presenting absolute as well as relative risk. Among otherwise healthy patients undergoing THA, the 15-year PJI risk was approximately 1% at normal weight, 2% with class III obesity, and 4% with class IV obesity; class IV obesity combined with multiple additional risk factors produced substantially higher absolute risk.23 3.3 Diabetes Mellitus and Hyperglycemia Diabetes was consistently associated with increased risk. Kong et al. reported a pooled OR of 1.58, while the Jamsen cohort found diabetes independently more than doubled infection risk (adjusted OR 2.3).6,14 The relationship is likely mediated by impaired neutrophil function, microvascular disease, reduced tissue oxygenation, altered collagen synthesis, and poorer wound healing. Risk appears particularly important when diabetes coexists with severe obesity. The literature therefore supports assessment of glycemic control before elective TJA. However, evidence is less consistent regarding a single HbA1c threshold that reliably distinguishes acceptable from unacceptable PJI risk. 3.4 Tobacco Use Tobacco exposure was associated with impaired tissue perfusion, delayed wound healing, and increased PJI. In a meta-analysis of 14 studies, tobacco users had approximately twice the odds of PJI compared with non-users (OR 2.02, 95% CI 1.47-2.77). Current smokers had an OR of 2.16, while former smokers had an OR of 1.52 compared with non-smokers. Current smokers also had greater risk than former smokers, supporting preoperative cessation.18 Kunutsor et al. similarly reported an RR of 1.83 for smokers compared with non-smokers.5 3.5 Malnutrition and Hypoalbuminemia Malnutrition emerged as one of the strongest modifiable risk categories. A meta-analysis including more than 250,000 patients reported that malnutrition was associated with an OR of 3.62 for PJI.27 A more recent synthesis reported an OR of approximately 3.44.36 Preoperative albumin is among the most frequently used nutritional biomarkers. Bohl et al. found hypoalbuminemia (<3.5 g/dL) associated with higher rates of surgical-site infection and adverse outcomes after TJA.17 A primary TJA study reported adjusted OR 4.69 for PJI among patients with low albumin.28 Recent data suggest that risk becomes particularly important at albumin concentrations below approximately 3.1 g/dL, although a single universal cutoff should not replace a complete nutritional assessment. 3.6 Preoperative Anemia Preoperative anemia was repeatedly associated with infection and transfusion risk. A cohort of 15,722 TJA patients demonstrated an association between anemia and subsequent PJI.29 Anemia may act through reduced tissue oxygenation and may also increase the probability of perioperative allogeneic transfusion, itself associated with postoperative infectious complications. Therefore, identification and correction of iron deficiency or other treatable causes of anemia may have benefits beyond reducing transfusion. 3.7 Rheumatoid Arthritis, Inflammatory Disease, and Immunosuppression Inflammatory arthropathy is associated with increased infection susceptibility through both disease-related immune dysfunction and immunosuppressive treatment. In the Mayo Clinic cohort, RA patients had a significantly higher PJI risk than matched patients with osteoarthritis (HR 4.08, 95% CI 1.35-12.33). Previous PJI and revision surgery further amplified risk.10 Meta-analyses reported more modest pooled associations, including an OR of approximately 1.57 for RA.6 Steroid and other immunosuppressive therapies also showed increased risk in several evidence syntheses.4-6 3.8 Male Sex and Medical Comorbidity Male sex has shown a reproducible association with PJI. Kunutsor et al. reported a pooled RR of 1.36, while Kong et al. reported an OR of 1.48.5,6 Large TKA registry data demonstrated an HR of 1.89 for male sex, while the Canadian THA cohort found an HR of 1.43.16,20 The reasons are probably multifactorial and may include differences in comorbidity, skin colonization, body composition, occupational exposure, and health behavior. High overall medical burden is also important. Medicare data identified congestive heart failure, chronic pulmonary disease, anemia, diabetes, depression, renal disease, peripheral vascular disease, rheumatological disease, metastatic disease, and valvular disease among predictors of PJI after TKA.13 3.9 ASA Physical-Status Classification Higher ASA classification represents cumulative systemic disease rather than one specific mechanism. Kong et al. reported a pooled OR of 2.06 for ASA >2.6 Namba et al. reported an HR of 1.65 for ASA >=3 in primary TKA.16 ASA status therefore provides useful global risk information but is less actionable than the individual conditions responsible for the elevated score. 3.10 Urinary Tract Infection and Asymptomatic Bacteriuria The relationship between urinary infection and PJI is complex. A meta-analysis reported a significantly higher PJI risk in patients with UTI (RR 3.17, 95% CI 2.19-4.59).30 More recent evidence suggests that timing is important, with UTI occurring within approximately two weeks before arthroplasty associated with greater risk. Asymptomatic bacteriuria is more controversial. A 2024 meta-analysis of 12 studies and 42,592 patients reported OR 3.47 for PJI in patients with ASB, but the organisms responsible for subsequent PJIs usually differed from organisms found in urine. Antibiotic treatment of ASB did not significantly reduce PJI.24 A 2026 meta-analysis likewise found increased pooled odds of PJI (OR 2.41) but no clear benefit of treating ASB before elective arthroplasty.31 These findings suggest that ASB may function partly as a marker of host vulnerability rather than a direct microbiological source of PJI. 3.11 Staphylococcus aureus and MRSA Colonization Staphylococci remain major pathogens in PJI, making preoperative colonization clinically important. Recent meta-analytic evidence indicates that patients colonized with MRSA retain an increased risk of PJI even when standard decolonization protocols are used.26 Preoperative screening and decolonization remain widely incorporated into arthroplasty pathways; however, colonization may identify a persistently higher-risk host who requires appropriate antimicrobial prophylaxis and surveillance. 3.12 Previous Joint Infection, Previous Surgery, and Cellulitis Previous surgery around the joint increases technical complexity, scar burden, operative duration, and the possibility of retained hardware or altered soft tissues. Previous joint surgery was associated with increased PJI in pooled analyses.4,5 The Finnish RA cohort demonstrated an HR of 5.49 for patients with a previous PJI of the same joint.10 Recent data also identified previous cellulitis as a relevant risk factor. In a national cohort of 105,926 patients, previous lower-extremity cellulitis was associated with a 2.4-fold greater odds of PJI after TKA; cellulitis occurring within one year of surgery conferred particularly high risk.32 3.13 Operative Duration Prolonged operative duration was one of the most consistent procedure-related factors. Namba et al. reported approximately 9% greater deep infection risk for each additional 15 minutes of TKA operative time.16 A 2024 meta-analysis of 17 studies involving 427,361 patients found that surgery lasting at least 90 minutes was associated with an OR of 1.50 for PJI, while procedures lasting at least 120 minutes had an OR of 1.56.22 Longer surgery may reflect procedural complexity while simultaneously increasing wound exposure, tissue handling, bacterial contamination opportunity, blood loss, and staff movement. 3.14 Blood Transfusion and Blood Conservation Several studies linked allogeneic transfusion with infection. A meta-analysis of six studies involving 21,770 patients found higher surgical-site infection rates among transfused patients, with pooled OR 1.71.33 Everhart et al. demonstrated a dose-dependent relationship: infection risk increased progressively with one, two, three, and more than three units of allogeneic red cells.34 A large case-control analysis similarly reported adjusted ORs of approximately 1.9 for superficial infection and 1.6 for deep infection among transfused patients.35 These findings support preoperative anemia correction, tranexamic acid use where appropriate, meticulous hemostasis, and evidence-based transfusion thresholds. 3.15 Wound-Related Factors Wound dehiscence, superficial surgical-site infection, persistent drainage, and other wound complications were repeatedly associated with subsequent deep infection.4,9,12 These factors may represent both direct routes of bacterial entry and indicators of impaired host healing. Early identification and structured management of wound complications therefore remain central to PJI prevention. 3.16 Factors With Inconsistent or Limited Evidence Not all commonly suspected factors demonstrate consistent associations. Age has shown variable findings, with some analyses suggesting no significant association and others suggesting that younger patients may have slightly greater risk, potentially because of underlying diagnoses or activity patterns.5,6 Hypertension, hyperlipidemia, hypothyroidism, liver disease, vitamin D deficiency, drainage practices, cement fixation, and alcohol intake have produced heterogeneous results. Vitamin D deficiency is biologically plausible and has been associated with poorer outcomes in some studies, but a recent multicenter study found no significant difference in PJI after perioperative vitamin D supplementation despite reductions in some superficial wound complications. Table 2. Summary of major risk factors and published effect estimates. Risk factor Published association Evidence interpretation BMI >=30 kg/m2 RR 1.60 (1.29-1.99)5 Consistent increased risk BMI >=40 kg/m2 RR 3.68 (2.25-6.01)5 Strong dose-related association Diabetes mellitus OR ~1.58 in meta-analysis6 Consistent increased risk Male sex RR 1.36; OR 1.485,6 Consistent modest increase Tobacco use OR 2.02 (1.47-2.77)18 Modifiable risk Rheumatoid arthritis OR 1.57 (1.30-1.88)6 Increased risk ASA >2 OR 2.06 (1.77-2.39)6 Marker of systemic disease burden Malnutrition OR approximately 3.4-3.627,36 Strong potentially modifiable association Low albumin Adjusted OR up to 4.69 in primary study28 Important nutritional marker Asymptomatic bacteriuria OR 2.41-3.4724,31 Association present; causality uncertain Symptomatic UTI RR 3.17 in one meta-analysis30 Active infection should be treated Operative time >=90 min OR 1.5022 Modifiable procedural factor Operative time >=120 min OR 1.5622 Increased risk Allogeneic transfusion Pooled OR 1.71 for SSI33 Supports blood conservation Prior cellulitis OR 2.432 Particularly relevant when recent Prior PJI HR 5.49 in RA cohort10 Strong historical risk marker Table 3. Practical classification of PJI risk factors. Category Risk factors Potential optimization Metabolic Obesity, diabetes, perioperative hyperglycemia Weight management; optimize glycemia Nutritional Hypoalbuminemia, malnutrition, vitamin deficiencies Nutritional assessment and supplementation Hematological Anemia, coagulopathy Treat anemia; blood-conservation pathway Behavioral Smoking/tobacco use, excessive alcohol Smoking cessation; alcohol-risk assessment Immune/inflammatory RA, systemic inflammatory disease, corticosteroids, immunosuppressants Coordinate immunomodulatory therapy Infectious Active UTI, MRSA colonization, recent cellulitis, previous PJI Treat active infection; screening/decolonization where indicated Comorbidity burden Renal, pulmonary, cardiovascular disease; high ASA Multidisciplinary medical optimization Surgical history Previous joint surgery, revision history Risk counseling and surgical planning Procedural Prolonged operative time, transfusion, wound complications Operative efficiency, hemostasis, blood management, wound surveillance

4.1 Principal Findings This systematic review demonstrates that PJI following TJA results from an interaction between host susceptibility, microbial exposure, and procedural factors. No single variable adequately predicts infection. Instead, risk accumulates across metabolic, nutritional, immunological, infectious, and surgical domains. Obesity emerged as the most consistently established patient-related factor, which is consistent with the AAOS evidence-based guideline.1 Diabetes, tobacco use, inflammatory disease, hypoalbuminemia, anemia, previous surgery, and immunosuppression were also repeatedly associated with PJI across independent evidence syntheses. The findings also demonstrate the importance of considering combinations of risk factors. Severe obesity may carry only a modest absolute infection probability in an otherwise healthy individual but substantially greater absolute risk when combined with diabetes, kidney disease, smoking, or immunosuppression.23 4.2 Obesity and Metabolic Dysfunction Obesity likely contributes through several mechanisms, including larger surgical exposure, longer operative duration, impaired tissue perfusion, increased dead space, chronic inflammation, wound tension, and associated metabolic disease. The pronounced increase in risk at very high BMI supports a nonlinear rather than purely linear relationship. This has implications for counseling. Patients should be informed of both relative and absolute risk rather than being given a single BMI-based binary classification. Importantly, evidence that weight reduction immediately before TJA necessarily normalizes PJI risk is less robust than evidence demonstrating the association between obesity and infection. Optimization should therefore emphasize global metabolic health rather than BMI in isolation. 4.3 Diabetes and Glycemic Control The association between diabetes and PJI has been reproduced in institutional cohorts, registries, and meta-analyses.5,6,14,16 Hyperglycemia adversely affects leukocyte function, collagen synthesis, vascular integrity, and wound healing. Preoperative counseling should therefore include assessment of diabetic control and perioperative glucose-management plans. However, defining one universally safe HbA1c threshold remains problematic because infection risk is continuous and influenced by accompanying obesity, renal disease, nutritional state, and perioperative glycemia. 4.4 Nutrition and Anemia as Underrecognized Risk Domains Malnutrition showed one of the largest associations in the review. This is clinically important because patients with obesity may simultaneously be malnourished, making visual assessment or BMI alone inadequate. Albumin is inexpensive and widely available but is influenced by inflammation, hepatic function, renal disease, and acute illness. It should therefore be interpreted as a marker of physiological reserve rather than an isolated nutritional diagnosis. Likewise, anemia can be both a marker of chronic disease and a modifiable hematological abnormality. Treating iron deficiency and reducing allogeneic transfusion may address multiple pathways associated with postoperative infection. 4.5 Smoking The tobacco findings provide one of the clearest examples of a modifiable behavioral risk factor. Current smokers experienced greater risk than former smokers, supporting the biological and clinical rationale for cessation before elective arthroplasty.18 Smoking cessation interventions should therefore be integrated into preoperative optimization rather than offered only as general health advice. 4.6 Infection and Colonization Active infection represents an important but heterogeneous category. Symptomatic UTI should be distinguished from asymptomatic bacteriuria. The evidence supporting an association between ASB and PJI does not demonstrate that the urinary organism directly seeds the implant. The frequent lack of microbiological concordance and failure of ASB antibiotic treatment to reduce PJI support this distinction.24,31 MRSA colonization is more directly relevant because Staphylococcus aureus is a common PJI pathogen. Contemporary evidence indicates that decolonization may reduce but not fully eliminate the excess risk of PJI among MRSA-positive patients.26 Recent cellulitis should similarly be considered during preoperative assessment, particularly when the affected limb is involved. 4.7 Operative Duration Prolonged operative time likely reflects both procedure complexity and a direct exposure effect. The consistent increase in PJI with procedures exceeding 90-120 minutes provides a practical quality-improvement target.22 Operative efficiency should not be interpreted as rushing surgery. Rather, appropriate preoperative planning, experienced teams, availability of equipment, management of difficult exposure, and avoidance of unnecessary delays can reduce preventable operative prolongation. 4.8 Blood Transfusion The relationship between transfusion and infection may reflect immunomodulation, greater operative blood loss, anemia, longer surgery, or more complex procedures. Nevertheless, the dose-response relationship reported in several studies strengthens the association. Patient blood-management strategies, including anemia correction, tranexamic acid, meticulous hemostasis, and restrictive evidence-based transfusion thresholds, therefore have plausible infection-prevention benefits. 4.9 Risk Should Be Viewed Cumulatively One of the most important findings is that PJI risk should not be reduced to a single factor such as BMI or HbA1c. A patient with moderate obesity but no diabetes, no smoking, normal albumin and hemoglobin, and low ASA status may have a different absolute risk from a patient with the same BMI plus diabetes, renal disease, tobacco exposure, immunosuppression, and malnutrition. Future risk models should therefore combine variables rather than applying isolated exclusion thresholds. 4.10 Clinical Implications The preoperative arthroplasty pathway should include structured evaluation of weight and metabolic status; diabetes and perioperative glucose control; tobacco exposure; nutritional status and serum albumin where appropriate; hemoglobin and treatable anemia; inflammatory disease and immunosuppressive therapy; active urinary, skin, dental, or systemic infection when clinically indicated; Staphylococcus aureus/MRSA colonization according to local protocols; history of previous surgery or PJI; and anticipated procedural complexity. The AAOS guideline similarly recognizes obesity as a moderately supported risk factor and identifies diabetes, anemia, tobacco use, malnutrition, inflammatory arthritis, renal disease, liver disease, mental-health disorders, immunocompromise, and prior infection among conditions associated with increased PJI risk, albeit with lower evidence strength for many factors.1 4.11 Strengths The review integrates evidence from meta-analyses, large registries, population-based cohorts, and recent studies through 2026. It evaluates host and procedural factors together and distinguishes consistently demonstrated associations from emerging or controversial findings. The review also emphasizes effect magnitude and clinical modifiability rather than treating all statistically associated factors as equally important. 4.12 Limitations Most available studies were observational, making residual confounding unavoidable. Definitions of PJI, follow-up duration, arthroplasty type, and risk-factor thresholds varied substantially. Several published meta-analyses reused overlapping registry or institutional cohorts. Therefore, their pooled sample sizes should not be interpreted as independent patients across reviews. Some reported associations may represent markers of underlying illness rather than directly causal factors. For example, hypoalbuminemia, prolonged hospitalization, and blood transfusion may partly reflect greater disease severity. A new meta-analysis was not performed in the present review because the aim was broad risk-factor synthesis and because substantial overlap existed between previously published quantitative reviews. 4.13 Future Research Future research should prioritize prospective multicenter studies evaluating combinations of risk factors and the impact of successful optimization. It is not sufficient to show that obesity, diabetes, anemia, or malnutrition correlate with PJI. Studies should determine whether interventions that modify these factors actually reduce infection incidence. Additional priorities include standardized reporting of absolute risk, external validation of multivariable risk calculators, assessment of interaction between risk factors, and evaluation of cost-effectiveness of optimization pathways.

Periprosthetic joint infection following total joint arthroplasty is a multifactorial complication arising from the interaction of host susceptibility, infectious exposures, and perioperative factors. The most consistently supported risk factors include obesity, diabetes mellitus, tobacco use, male sex, rheumatoid and systemic inflammatory disease, immunosuppression, malnutrition/hypoalbuminemia, anemia, previous joint surgery or infection, symptomatic infection, and higher medical comorbidity. Prolonged operative duration, blood transfusion, and wound complications further increase postoperative risk. Among these variables, obesity, glycemic control, tobacco exposure, nutritional deficiency, anemia, active infection, medication-related immunosuppression, operative efficiency, and perioperative blood management offer meaningful opportunities for modification. Accordingly, prevention of PJI should move from isolated risk-factor thresholds toward individualized, multidimensional preoperative optimization and cumulative risk assessment.

1. American Academy of Orthopaedic Surgeons. Diagnosis and Prevention of Periprosthetic Joint Infections: Evidence-Based Clinical Practice Guideline. AAOS; 2019. 2. McMaster Arthroplasty Collaborative. Risk Factors for Periprosthetic Joint Infection Following Primary Total Hip Arthroplasty: A 15-Year, Population-Based Cohort Study. J Bone Joint Surg Am. 2020;102(6):503-509. doi:10.2106/JBJS.19.00537. 3. McMaster Arthroplasty Collaborative. Incidence and Predictors of Prosthetic Joint Infection Following Primary Total Knee Arthroplasty: A 15-Year Population-Based Cohort Study. J Arthroplasty. 2022;37(2):367-372.e1. 4. Zhu Y, Zhang F, Chen W, Liu S, Zhang Q, Zhang Y. Risk factors for periprosthetic joint infection after total joint arthroplasty: a systematic review and meta-analysis. J Hosp Infect. 2015;89(2):82-89. doi:10.1016/j.jhin.2014.10.008. 5. Kunutsor SK, Whitehouse MR, Blom AW, Beswick AD, INFORM Team. Patient-Related Risk Factors for Periprosthetic Joint Infection after Total Joint Arthroplasty: A Systematic Review and Meta-Analysis. PLoS One. 2016;11(3):e0150866. doi:10.1371/journal.pone.0150866. 6. Kong L, Cao J, Zhang Y, Ding W, Shen Y. Risk factors for periprosthetic joint infection following primary total hip or knee arthroplasty: a meta-analysis. Int Wound J. 2017;14(3):529-536. doi:10.1111/iwj.12640. 7. Ren X, Ling L, Qi L, et al. Patients' risk factors for periprosthetic joint infection in primary total hip arthroplasty: a meta-analysis of 40 studies. BMC Musculoskelet Disord. 2021. 8. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. 9. Pulido L, Ghanem E, Joshi A, Purtill JJ, Parvizi J. Periprosthetic joint infection: the incidence, timing, and predisposing factors. Clin Orthop Relat Res. 2008. 10. Bongartz T, Halligan CS, Osmon DR, et al. Incidence and risk factors of prosthetic joint infection after total hip or knee replacement in patients with rheumatoid arthritis. Arthritis Rheum. 2008;59(12):1713-1720. doi:10.1002/art.24060. 11. Malinzak RA, Ritter MA, Berend ME, Meding JB, Olberding EM, Davis KE. Morbidly obese, diabetic, younger, and unilateral joint arthroplasty patients have elevated total joint arthroplasty infection rates. J Arthroplasty. 2009;24(6 Suppl):84-88. 12. Jamsen E, Huhtala H, Puolakka T, Moilanen T. Risk factors for infection after knee arthroplasty: a register-based analysis of 43,149 cases. J Bone Joint Surg Am. 2009. 13. Bozic KJ, Lau E, Kurtz S, Ong K, Berry DJ. Patient-related risk factors for postoperative mortality and periprosthetic joint infection in Medicare patients undergoing TKA. Clin Orthop Relat Res. 2012;470(1):130-137. doi:10.1007/s11999-011-2043-3. 14. Jamsen E, Nevalainen P, Eskelinen A, Huotari K, Kalliovalkama J, Moilanen T. Obesity, diabetes, and preoperative hyperglycemia as predictors of periprosthetic joint infection. J Bone Joint Surg Am. 2012;94(14):e101. doi:10.2106/JBJS.J.01935. 15. Bozic KJ, Lau E, Kurtz S, et al. Patient-related risk factors for periprosthetic joint infection and postoperative mortality following total hip arthroplasty in Medicare patients. J Bone Joint Surg Am. 2012;94(9):794-800. 16. Namba RS, Inacio MCS, Paxton EW. Risk factors associated with deep surgical site infections after primary total knee arthroplasty: an analysis of 56,216 knees. J Bone Joint Surg Am. 2013;95(9):775-782. doi:10.2106/JBJS.L.00211. 17. Bohl DD, Shen MR, Kayupov E, Della Valle CJ. Hypoalbuminemia independently predicts surgical site infection, pneumonia, length of stay, and readmission after total joint arthroplasty. J Arthroplasty. 2016;31(1):15-21. 18. Bedard NA, DeMik DE, Owens JM, Glass NA, DeBerg J, Callaghan JJ. Tobacco use and risk of wound complications and periprosthetic joint infection: a systematic review and meta-analysis. J Arthroplasty. 2019;34(2):385-396.e4. doi:10.1016/j.arth.2018.09.089. 19. Zhong J, Wang B, Chen Y, et al. Relationship between body mass index and the risk of periprosthetic joint infection after primary total hip or knee arthroplasty. Ann Transl Med. 2020. 20. McMaster Arthroplasty Collaborative. Risk Factors for Periprosthetic Joint Infection Following Primary Total Hip Arthroplasty. J Bone Joint Surg Am. 2020;102:503-509. 21. McMaster Arthroplasty Collaborative. Incidence and Predictors of Prosthetic Joint Infection Following Primary Total Knee Arthroplasty. J Arthroplasty. 2022;37:367-372.e1. 22. Shin KH, Kim JH, Han SB. Greater Risk of Periprosthetic Joint Infection Associated with Prolonged Operative Time in Primary Total Knee Arthroplasty: Meta-Analysis of 427,361 Patients. J Clin Med. 2024;13(11):3046. doi:10.3390/jcm13113046. 23. Carender CN, et al. Obesity and Primary Total Hip Arthroplasty: The Absolute versus Relative Risk of Periprosthetic Joint Infection at 15 Years. J Arthroplasty. 2024. 24. Ghaseminejad-Raeini A, Esmaeili S, Ghaderi A, et al. Is asymptomatic bacteriuria a noticeable risk factor for periprosthetic joint infection following total joint arthroplasty? Arch Orthop Trauma Surg. 2024;144(12):5205-5216. doi:10.1007/s00402-024-05415-1. 25. Erling AM, Zhao AY, Marrache M, Das A, Thakkar SC, Golladay GJ. Prior Cellulitis as a Risk Factor for Periprosthetic Joint Infection in Total Knee Arthroplasty. J Arthroplasty. 2026;41(3):907-910. 26. Javidmehr S, Mortazavi SMJ, Rastegar M, et al. Preoperative Methicillin-Resistant Staphylococcus aureus Colonization and Risk of Periprosthetic Joint Infection after Total Joint Arthroplasty: A Systematic Review and Meta-Analysis. J Arthroplasty. 2026. doi:10.1016/j.arth.2026.07.042. 27. Yuwen P, Chen W, Lv H, et al. Association of malnutrition with periprosthetic joint and surgical site infections after total joint arthroplasty: a systematic review and meta-analysis. J Hosp Infect. 2019. 28. Tan TL, et al. Malnutrition and the development of periprosthetic joint infection in patients undergoing primary elective total joint arthroplasty. J Arthroplasty. 2018. 29. Greenky M, Gandhi K, Pulido L, Restrepo C, Parvizi J. Preoperative anemia in total joint arthroplasty: is it associated with periprosthetic joint infection? Clin Orthop Relat Res. 2012. 30. Wang C, et al. Effect of urinary tract infection on the risk of prosthetic joint infection: a systematic review and meta-analysis. Surgeon. 2020. 31. Roy V, Van Brenk A, Benaroch LR, et al. Asymptomatic Bacteriuria and Periprosthetic Joint Infection Risk: A Systematic Review and Meta-Analysis. J Arthroplasty. 2026. doi:10.1016/j.arth.2026.03.046. 32. Erling AM, et al. Prior Cellulitis as a Risk Factor for Periprosthetic Joint Infection in Total Knee Arthroplasty. J Arthroplasty. 2026. 33. Kim JL, Park JH, Han SB, Cho IY, Jang KM. Allogeneic Blood Transfusion Is a Significant Risk Factor for Surgical-Site Infection Following Total Hip and Knee Arthroplasty: A Meta-Analysis. J Arthroplasty. 2017;32(1):320-325. doi:10.1016/j.arth.2016.08.026. 34. Everhart JS, Sojka JH, Mayerson JL, Glassman AH, Scharschmidt TJ. Perioperative Allogeneic Red Blood-Cell Transfusion Associated with Surgical Site Infection After Total Hip and Knee Arthroplasty. J Bone Joint Surg Am. 2018;100(4):288-294. doi:10.2106/JBJS.17.00237. 35. Frisch NB, et al. Association between allogeneic blood transfusion and wound infection after total hip or knee arthroplasty: a retrospective case-control study. J Bone Jt Infect. 2019. 36. Association between malnutrition status and total joint arthroplasty periprosthetic joint infection and surgical site infection: a systematic review meta-analysis. 2024.