Risk Factors for Infection in Total Knee Arthroplasty: A Narrative Review according of the ICM Istanbul 2025 | Lo Scalpello - Journal

Abstract

Periprosthetic joint infection (PJI) after total knee arthroplasty (TKA) remains one of the most serious complications in modern orthopedics. Despite technological and surgical advances, its incidence remains stable, suggesting that prevention cannot rely exclusively on the surgical act.

The 2025 International Consensus on Musculoskeletal Infections (ICM) held in Istanbul devoted extensive space to the analysis of preoperative risk factors, emphasizing the central role of the host and preoperative optimization.

This narrative review systematically analyzes the main risk factors for infection in patients undergoing TKA, distinguishing between modifiable and non-modifiable factors, and discusses the practical implications for daily clinical management in light of the most recent ICM recommendations.

Introduction

Total knee arthroplasty (TKA) is one of the most commonly performed procedures and one with the greatest impact on patient quality of life. However, periprosthetic joint infection (PJI) continues to be a devastating complication, often associated with multiple reoperations, functional failure, and significant emotional burden for the patient.

In recent years, a broader vision of PJI has progressively emerged, no longer considered exclusively as a technical complication, but rather as the result of a complex interaction between:

1. biological characteristics of the host;
2. microbial load and virulence;
3. procedural and organizational factors.

The 2025 ICM Consensus constitutes a further step forward in this direction, reaffirming that prevention of infection begins before surgery through identification and correction of preoperative risk factors.

Methodology and rationale of the review

This narrative review is based on the analysis of official ICMORTHO 2025 documents, with particular reference to the working groups dedicated to SSI/PJI risk factors (G13, G14, G17, HK1), integrated with the literature cited in the proceedings and in the subsequent summary articles.

The aim is not to provide a quantitative meta-analysis, but rather to offer a critical, clinically oriented interpretation that is applicable to daily orthopedic practice.

The concept of “host optimization” according to ICM 2025

The concept of host optimization constitutes one of the fundamental pillars of the modern approach to the prevention and treatment of musculoskeletal infections, particularly periprosthetic infections. This term refers to the set of strategies aimed at identifying, correcting, and stabilizing patient-related risk factors (host factors) that may compromise immune response, tissue healing, and surgical outcomes.

ICM 2025 reiterates that the success of an orthopedic procedure – especially in prosthetic surgery – depends not only on surgical technique or microbiological control, but also on the biological quality of the host receiving the implant. The patient is therefore not a passive element, but a determining variable in the delicate balance between bacterial colonization and immune defense.

Host optimization includes correction of modifiable factors such as glycemic control in diabetes, smoking cessation, improvement of nutritional status, management of obesity, treatment of anemia, suspension or modulation of immunosuppressive therapies when possible, and stabilization of systemic comorbidities. At the same time, it acknowledges the existence of non-modifiable factors (age, chronic diseases, biological frailty) that must be integrated into risk stratification and therapeutic strategy selection.

From this perspective, host optimization is not a single preoperative act but a continuous process that begins before surgery, continues throughout the perioperative period, and extends into follow-up. The ultimate goal is to transform an “unfavorable” host into a biologically more competent one, reducing infection risk and improving the likelihood of surgical success.

One of the central messages of the Consensus is that most patients undergoing TKA present at least one modifiable risk factor.

This seemingly simple fact has profound practical implications: surgery should not be considered an isolated event, but the final step of an optimization pathway.

The concept of “patient readiness for surgery” is introduced, emphasizing that infection risk reduction requires careful biological preparation of the patient.

Diabetes mellitus and glycemic control

Diabetes is one of the most studied risk factors for PJI, but the Consensus highlights a crucial aspect: it is not the diagnosis of diabetes itself that determines risk, but the level of metabolic control.

Group G17 emphasizes that no single marker is universally ideal. HbA1c, fructosamine, and perioperative glucose measurements provide complementary information.

In particular:

1. HbA_1c is widely used but has limitations due to its historical nature;
2. fructosamine reflects glycemic control over the previous 2–3 weeks and has shown good correlation with infectious complications;
3. perioperative glycemic variability is emerging as an additional prognostic element.

The practical message is clear: glycemic control should be evaluated dynamically and individually, and not reduced to a rigid threshold.

Obesity constitutes an independent risk factor for infection after TKA.

The Consensus clarifies that risk is not linked exclusively to body mass index, but to a combination of:

1. reduced perfusion of adipose tissue,
2. increased dead space,
3. greater difficulty in wound management,
4. longer surgical times.

Obesity is frequently associated with other unfavorable conditions (diabetes, malnutrition, anemia), amplifying overall risk.

When possible, the recommendation is to implement weight reduction and metabolic optimization programs before surgery.

Preoperative anemia

Group G14 of the ICM 2025 Consensus provides some of the strongest quantitative evidence.

The meta-analyses reviewed demonstrate that preoperative anemia is associated with a significant increase in SSI and PJI risk in major orthopedic surgeries, including TKA.

Anemia contributes to risk through several mechanisms:

1. reduced tissue oxygenation,
2. higher likelihood of allogeneic transfusion,
3. presence of underlying systemic comorbidities.

The Consensus reinforces the concept of patient blood management, recommending identification and treatment of anemia prior to surgery.

Malnutrition

Malnutrition is frequently underdiagnosed, especially in elderly or frail patients.

The ICM 2025 Consensus recognizes hypoalbuminemia and nutritional deficiencies as significant risk factors for infection, emphasizing their impact on immune response and surgical wound healing.

Nutritional screening and preoperative correction are considered simple but high-impact preventive interventions.

Smoking

Smoking remains one of the most relevant modifiable risk factors.

The Consensus highlights how vasoconstriction, reduced oxygenation, and impaired neutrophil function contribute to increased risk of wound infection and PJI.

Smoking cessation at least four weeks before surgery is considered an effective risk-reduction strategy.

Immunosuppression and chronic inflammatory diseases

Patients with rheumatoid arthritis or other chronic inflammatory diseases have an increased risk of infection that is related both to the underlying disease and immunosuppressive therapies.

The ICM 2025 Consensus does not propose rigid exclusions, but emphasizes the need for personalized management of biologic agents and corticosteroids in collaboration with the referring specialist.

Bacterial colonization and infectious foci

Colonization with Staphylococcus aureus, particularly MRSA, constitutes a well-documented risk factor.

The Consensus supports preoperative screening and decolonization programs, especially in high-risk patients.

Similarly, urinary, cutaneous, or dental infections must be identified and treated before surgery.

Preoperative intra-articular injections

Group HK1 of the ICM 2025 Consensus specifically addresses intra-articular injections.

The reviewed literature shows an increased risk of PJI when TKA is performed within 3 months of an intra-articular injection.

The determining factor is not the type of injection, but its timing.

Beyond 3 months, the risk tends to overlap with that of non-injected patients.

Care pathway–related factors

The Consensus highlights that the care pathway also influences infection risk:

1. length of hospital stay;
2. wound management;
3. continuity of care after discharge;
4. recovery environment.

These elements, although often considered “organizational”, significantly contribute to the overall risk balance.

Discussion

The 2025 Istanbul Consensus constitutes both an endpoint and a new beginning in the management of periprosthetic infections. More than a simple revision of diagnostic criteria or therapeutic algorithms, it stands as a mature synthesis of 20 years of conceptual evolution, in which the international orthopedic community has progressively abandoned rigid certainties to embrace a more dynamic, probabilistic, and multidimensional approach.

One of the most significant aspects is the definitive overcoming of the binary diagnostic concept. PJI is no longer viewed as a condition that is either “present or absent”, but as a biological spectrum in which diagnostic probability increases with the convergence of multiple elements: clinical, serological, microbiological, histological, and intraoperative. This concept, already introduced in previous consensuses, finds in Istanbul a clearer and more applicable formalization for daily clinical practice. Diagnosis is no longer a court issuing a verdict, but a process of evidence accumulation requiring competence, experience, and interpretative ability.

In this sense, the 2025 Consensus reinforces the role of the surgeon not only as a procedural executor but as a clinical interpreter. Criteria do not replace judgment; they guide it. This is a strong cultural message that restores centrality to the physician and their decision-making responsibility, especially in the “gray zones” that now represent the real challenge of PJI.

On the diagnostic level, Istanbul 2025 confirms the central role of biomarkers but downscales their isolated use. No single test is sufficient. Even the most promising markers (such as α-defensin, calprotectin, or new molecular panels) must be interpreted in a clinical context, avoiding the illusion of a technological shortcut. This constitutes a a high level of scientific maturity: the Consensus recognizes the limits of technology and calls for interpretative caution, especially in an era where overdiagnosis is a real risk.

From a therapeutic standpoint, the Istanbul 2025 document definitively marks the end of the “one size fits all” dogma. DAIR, one-stage, and two-stage are no longer competing strategies, but complementary tools to be used based on patient, microorganism, implant stability, soft tissues, and infection timing. The algorithm is not a rigid ladder, but a flexible map. This personalized approach probably constitutes the true leap forward compared to previous consensuses.

Particularly relevant is the message on the importance of biological timing: not only when to intervene, but how to interpret the moment of infection in its dialogue with the host. The 2025 Consensus encourages considering PJI as a disease of host–implant–microorganism interaction, rather than as an isolated mechanical event. This concept has profound implications, especially for DAIR selection, which is no longer judged solely by elapsed days, but by tissue vitality and real inflammatory response.

Another aspect of major value is the strengthening of the multidisciplinary model. Istanbul 2025 recognizes that no surgeon, regardless of experience, can manage the complexity of PJI alone. Infectious disease specialists, microbiologists, pathologists, anesthesiologists, radiologists, and specialized nurses are not accessory figures, but integral to therapeutic success. This approach is not merely organizational but ethical: it places the patient at the center of a system of interacting expertise.

The Consensus does not hide current limitations. Many recommendations are still based on moderate or low levels of evidence, and this is not a failure but an act of scientific honesty. PJI remains a condition in which biological variability often exceeds the ability of randomized studies to provide definitive answers. In this sense, Istanbul 2025 is also an invitation to research: not to produce more data, but better data, more homogeneous, more comparable, and more focused on patient-relevant outcomes.

The review of the ICM 2025 documents highlights a paradigm shift:

PJI prevention is not a surgical act, but a complex, multidisciplinary clinical process.

The orthopedic surgeon assumes a central role as coordinator of this pathway, integrating surgical, medical, and organizational competencies.

Conclusions

In conclusion, the Istanbul 2025 Consensus is not an instruction manual, but a cultural framework. It provides tools, common language, and shared principles. Above all, it invites the surgeon to return to being a clinician, a thinker, and a responsible decision-maker. It is a Consensus that does not simplify complexity, but teaches how to inhabit it. And for those who have fought periprosthetic infections in the field for years, this is not only scientific progress, but an act of respect toward the reality of our profession.

It reinforces a key concept: TKA is safer the better the biological ground on which it is implanted.

Identification and correction of preoperative risk factors now represent one of the most effective tools to reduce infection incidence and improve long-term outcomes.

Conflict of interest statement

The authors declare no conflict of interest.

Funding

None

Authors’ contributions

The Authors contributed equally to the work.

Ethical consideration

Ethical approval was not required for this study, as it is a narrative review based exclusively on previously published data and does not involve new studies on human participants or animals performed by the authors. Informed consent was not required..

History

Received: February 5, 2026

Accepted: May 15, 2025

Published online: June 12, 2026

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