Management of Periprosthetic Infection: Review of Current Literature and Management Algorithm

Keywords

periprosthetic joint infection - DAIR - two-stage surgical revision - one-stage surgical revision - hip arthroplasty infection

Introduction

Periprosthetic infection is estimated to occur in 1-2% of all prosthetic surgery patients. The paradigm for managing this challenging condition lies in a thorough understanding of the role biofilm plays in the process. In 1983, Dr. Insall and colleagues first published how they successfully resolved a prosthetic knee infection with a two-stage revision and replacement.[1] Later, the importance of biofilm would be discovered, and the reason why isolated antibiotic therapy is ineffective in the management of this entity.[2]

The development of biofilms on prosthetic surfaces is a process favored by the presence of the implant, which acts as an ideal substrate for bacterial adhesion. These organized bacterial communities hinder the effective penetration of antimicrobials, especially in the deeper layers.[3] As a result, in advanced cases, the dismantling of the prosthetic components is necessary, which increases both the patient's morbidity and mortality as well as healthcare costs, with an estimated economic impact of between $40,000 and $160,000 per case.[4] In fact, it has been estimated that the cost of a revision arthroplasty due to infection can be up to four times higher than that of a primary arthroplasty and twice that of an aseptic revision, representing a significant burden on healthcare systems.

Since biofilm maturation directly influences therapeutic strategy, determining the timing of its formation is crucial. Its degree of development, along with factors related to the patient and previous surgery, determines the management of infection in joint prostheses.[5] Traditionally, infections have been classified as acute or chronic according to their duration; however, this distinction is merely academic, since symptoms may overlap, and the duration of the infection varies ([Table 1]).

Table 1

Characteristics	Acute Prosthetic Infection (Immature Biofilm)	Chronic Prosthetic Infection (Mature Biofilm)
Pathogeny	<4 weeks after surgery	≥4 weeks after surgery
Clinical features	Acute pain, fever, red and swollen joint, prolonged postoperative drainage	Chronic pain, prosthetic loosening, fistulous tract
Typical microorganisms	High virulence: S. aureus, gram-negative (E. coli, Klebsiella)	Low virulence: coagulase-negative staphylococci, C. acnes

This article addresses the critical importance of a protocolized approach and the application of early and specific measures in the management of periprosthetic joint infection. It highlights the need for diligent and coordinated intervention, based on scientific evidence, to enable the eradication of the infection while preserving joint function and improving the patient's quality of life after arthroplasty.

Therapeutic Strategies

DAIR

Implant-retaining debridement is an effective tool for managing acute postoperative infections and acute hematogenous infections in selected patients based on numerous meta-analyses, with success rates currently around 71%.[6] [7] [8]

In those patients with good skin condition, in whom the responsible microorganism has been identified, without it being polymicrobial, nor resistant to conventional antimicrobials available in the hospital center and provided that the duration of the onset of symptoms does not exceed 4-6 weeks[7] [8] ([Table 2]).

Table 2

Required criteria	Characteristics
Duration of symptoms	≤ 4-6 weeks.
Implant not mobilized	Stable on imaging tests.
Microorganism identified	Responsive to available antibiotics. Different from fungal, polymicrobial, or enterococcal infections.
Good soft tissue condition	No abscesses or fistulas.
Immunocompetent patient	No underlying immunosuppressive disease (rheumatic, hematologic, oncologic, etc.)

DAIR should not be considered an emergency procedure, since it is advisable to appropriately select the patient with potentially reversible clinical conditions such as coagulopathy, nutritional status, hyperglycemia, severe anemia, etc., and to have the modular elements that need to be replaced.[8] In patients presenting with septic shock whose primary cause is suspected to be periprosthetic infection, an emergent DAIR may be indicated to reduce the microbial load, although this is somewhat more debated.

DAIR Failure Prediction Scales

Currently, two scores stand out as useful tools for predicting DAIR failure: the KLIC score and the CRIME80 score. These have been validated in independent studies and cited in academic debates, such as the 2019 International Consensus on Prosthetic Infections, although they are not part of its official recommendations. Despite not being included in the most recent guidelines on the management of periprosthetic infections, both offer promising value in risk stratification and selection of patients for the procedure.[10] [11]

While the CRIME80 score provides information on the risk of DAIR failure in late acute infections, the KLIC score is more focused on the prognosis and risk of DAIR failure in acute postoperative infections. The KLIC score was developed by Tonero et al. and considers renal failure (K); liver cirrhosis (L); index surgery: primary or revision (I); and CRP (C), establishing a cutoff point of 4 ([Table 3]). On the other hand, we have the CRIME 80 score, developed by the study group for implant-associated infections (ESGIAI), within the European Society of Clinical Microbiology and Infectious Diseases. The variables that define it are: COPD (C); CRP; Rheumatoid Arthritis (R); index surgery: primary or revision (I); Male (M); Polyethylene change (E); Age over 80 years, assuming a cut-off point of 3. ([Table 4]).

Table 3

Variable	Score
C Chronic obstructive pulmonary disease (COPD)	1
CRP > 150 mg/L	1
R Rheumatoid arthritis	3
I Index surgery (following fracture)	3
M Male	1
E Polyethylene exchange	-1
> 80 years	2

Table 4

Microorganism	Initial treatment (IV)	Alternatives in case of allergy or resistance	Continuation treatment (VO)
Staphylococcus spp. (MSSA)	Cloxacillin or cefazolin	Glycopeptides (vancomycin/teicoplanin) or daptomycin	Levofloxacin + rifampin or (clindamycin/co-trimoxazole + rifampin) or ceftaroline (severe cases)
Staphylococcus spp. (MRSA)	Vancomycin (trough target 15-20 mg/L) or daptomycin (8-10 mg/kg)	Daptomycin + fosfomycin or ceftaroline	Co-trimoxazole or clindamycin + rifampin, or linezolid as monotherapy or daptomycin + fosfomycin followed by linezolid/co-trimoxazole/clindamycin
Streptococcus spp.	Beta-lactam (penicillin, ampicillin, cephalosporin except for Enterococcus)	Vancomycin or teicoplanin	Depending on the antibiogram; avoid amoxicillin for Enterococcus spp.
Enterococcus spp. (E. faecalis)	Ampicillin (if sensitive) or vancomycin	Teicoplanin or linezolid	Oral amoxicillin is not recommended due to high MICs
Gram negative bacilli (susceptible enterobacteria)	Third-generation cephalosporins (ceftriaxone)	Ertapenem if ESBL+	Fluoroquinolones (levofloxacin) or co-trimoxazole if sensitive
Pseudomonas aeruginosa	Piperacillin-Tazobactam, meropenem, or ceftazidime	Colistin or fosfomycin (depending on sensitivity)	Fluoroquinolones (ciprofloxacin)

Surgical Technique

A wide arthrotomy must first be performed to allow inspection of the entire cavity and remove both affected material and tissue, leaving no debris that could remain in any unexposed plane. Next, we will remove both necrotic tissue and tissue suggestive of infection. It is essential to collect at least five sterile samples during the surgical procedure, ensuring a complete microbiological analysis that allows identification of the causative agent and its antibiotic sensitivity profile. We will then perform a complete 360° synovectomy. Often, due to inadequate exposure of the posterior synovial tissue, infections persist and debridement with implant retention fails. We will achieve this in the case of modular knee prostheses, for example, by removing the mobile polyethylene component.[12] Subsequently, a thorough wash will be necessary, which has been established according to the latest international consensus guidelines at 9 liters of physiological saline solution.

Antibiotic Treatment

Treatment of any suspected infection should not begin before the microorganism has been identified, debridement has been performed, and samples have been collected in the operating room.

Generally, monotherapy regimen is not usually effective. For methicillin-sensitive staphylococci, the mainstay of treatment would include levofloxacin and rifampin, which could be replaced with rifampin plus clindamycin or cotrimoxazole. For methicillin-resistant staphylococci, vancomycin/daptomycin and rifampin could be used, or rifampin plus clindamycin/cotrimoxazole/fusidic acid. The addition of rifampin is an important independent predictor of treatment success due to its significant effect on biofilm resistance.[13] In cases of rifampin resistance or allergy, vancomycin or daptomycin followed by cotrimoxazole, linezolid, or clindamycin is valid; an alternative is daptomycin plus fosfomycin followed by linezolid, cotrimoxazole, or clindamycin. For susceptible gram-negative bacilli, a fluoroquinolone regimen should be initiated. For enterobacteriaceae, ceftriaxone or ertapenem followed by cotrimoxazole could also be used. For Pseudomonas aeruginosa infections, alternative treatment could be piperacillin-Tazobactam, meropenem, or colistin.

Treatment should be initiated with intravenous antibiotics due to their increased availability in the bloodstream for at least one week. Treatment can then be de-escalated to oral antibiotic therapy in the following weeks. Most studies recommend a total of six weeks,[14] [15] with serial testing of acute-phase reactants during this period, the most important of which is CRP. [Table 4] summarizes the different antibiotic therapy strategies and alternatives.

DAIR Failure

If the infection has not been eradicated by retaining the fixed components and performing extensive debridement, it is advisable to consider replacing them. Systematic reviews describe success rates for the second DAIR like those for the first, so a change in management strategy should be considered to avoid additional surgical procedures.[16] [17] A comparison with the indications of the main strategies is detailed in [Table 5].

Table 5

Variable	Score
K Chronic kidney failure (Kidney)	2
L Cirrhosis (Liver)	1,5
I Index surgery (revision or after femoral head fracture)	1,5
C Cementation	2
C CRP > 115 mg/L	2,5

Clinical Cases

To illustrate the application of the CRIME80 and KLIC scores in selecting patients for DAIR, two real clinical cases of acute periprosthetic infection following total knee arthroplasty (TKA) are presented.

Case 1

This is a 73-year-old patient with a history of type 2 diabetes mellitus, high blood pressure, and early chronic kidney disease who underwent total right knee arthroplasty for severe tricompartmental gonarthrosis. Fourteen days after surgery, she returned to the clinic for pin removal, at which time the presence of serosanguinous exudate was observed at the surgical wound, with no signs of gross dehiscence. The patient was afebrile, without systemic symptoms, although she had joint pain for the past few days and mild periincisional erythema ([Figure 1]).

Figure 1 Image two weeks after total knee arthroplasty. Periscarring erythema and exudate from the surgical wound are observed.

Laboratory tests revealed a CRP of 25 mg/L, ESR of 45 mm/h, and leukocytosis of 9,800/µL. Renal function tests showed a creatinine of 1.1 mg/dL with an estimated glomerular filtration rate of 65 ml/min. A joint puncture revealed a leukocyte count of 12,500/µL and a predominance of polymorphonuclear cells (92%), with no microorganisms seen on Gram stain. X-rays showed no signs of loosening prosthetics, and ultrasound revealed a joint effusion without organized collections.

Given the time of evolution of the infection, the stability of the prosthesis and the absence of poor prognostic factors, an evaluation was performed using the KLIC scale ([Table 6]), the result of which was 2.

Table 6

Characteristics of the microorganism	Guest characteristics
Organism identified preoperatively	Good bone stock
Organism susceptible to antibiotic therapy	Good soft tissue condition (no fistulas, good skin coverage)
	Immunocompetent
	No sepsis

A surgical intervention was scheduled with debridement and polyethylene exchange, and an intraoperative lavage with abundant saline was performed. Intraoperative cultures isolated the Staphylococcus epidermidis sensitive to vancomycin. The patient received intravenous vancomycin for six weeks, followed by oral rifampin and levofloxacin for three months. The outcome was favorable, with normalization of inflammatory markers and no signs of persistent infection.

Case 2

The second case involved an 81-year-old man with a history of hypertension and chronic obstructive pulmonary disease (COPD) who had undergone total right knee replacement for osteoarthritis of the knee. The patient presented five months after surgery with progressively increasing pain in the operated knee and the appearance of a seropurulent discharge. Medical history revealed a history of recurrent urinary tract infections within the previous 4 weeks, leading to suspicion of hematogenous dissemination.

On examination, the patient presented marked edema and erythema around the surgical wound, with purulent discharge. The patient was afebrile, although he reported general malaise and progressive functional impairment of the joint.

Laboratory tests revealed elevated CRP at 155 mg/L, ESR at 72 mm/h, and leukocytosis at 13,500/µL. Creatinine was 1.5 mg/dL, with an estimated glomerular filtration rate of 48 ml/min. Joint aspiration revealed a leukocyte count of 35,000/µL, with 95% polymorphonuclear cells, and Gram staining showed the presence of Gram-positive cocci. Radiography revealed early signs of loosening of the tibial component ([Figure 2]).

Figure 2 AP and lateral X-rays of the patient in case 2 showing early signs of loosening of the total knee prosthesis, with visible osteolysis in the medial tibial plateau and a double contour image in the lateral plateau.

The CRIME80 assessment revealed a score of 6, so the risk of DAIR failure was high, and it was decided to opt for a two-stage prosthetic revision.

Single-stage revision

Single-stage revision is an attractive option as it aims to resolve the infection while avoiding a second surgery, thus achieving lower surgical morbidity and mortality, faster functional recovery, and, consequently, an improvement in the patient's quality of life. Furthermore, it significantly reduces healthcare costs and, therefore, total healthcare expenditure.[18]

Another important advantage is the reduction in the duration of postoperative systemic antibiotic treatment, which decreases both side effects and the risk of developing antimicrobial resistance.[19]

However, single-stage revision does not apply to all patients, as there are specific selection criteria. The Second International Consensus Meeting on Musculoskeletal Infection, held in Philadelphia, established the following criteria[20]:

• · Non-immunocompromised patient.

• · Absence of systemic sepsis.

• · Minimal bone loss and soft tissue defect allowing for primary wound closure.

• · Identification of pathogens before surgery.

• · Known susceptibility of isolated microorganisms.

• Relative contraindications include severe soft tissue damage that prevents direct closure, presence of an unresectable fistula along with the scar from the initial intervention, joint infection with negative culture, inability to perform radical debridement or apply local antimicrobial treatment, and lack of adequate bone stock for fixation of the new implant ([Figure 4]).

Figure 3 Through the DAIR procedure, extensive debridement is performed, and the mobile components are replaced, in this case, the polyethylene, without removing the remaining prosthesis components.

Figure 4 Image of a fistula with three openings along the scar pathway of an infected hip prosthesis. Its presence contraindicates a one-stage revision.

In addition to the selection criteria, the key steps for the success of this technique include aggressive debridement of soft tissues, complete removal of the implants and primary cement, as well as the use of antibiotic-loaded cement at the time of revision, accompanied by a specific postoperative antibiotic therapy protocol. If these criteria and steps are properly applied, the outcomes can be comparable to - or even better than - those of two-stage exchange in preselected patients.[21]

Two-stage revision

In the remaining cases that do not fit any of the indications mentioned for the two previous techniques, we should opt for the gold standard, which will involve removing the components of the prosthesis, applying a spacer with antibiotics along with a regimen of intravenous and oral antibiotic therapy, and in another surgical procedure, implanting the new prosthesis.

Spacers

There are two main types of spacers: static, which prevents joint movement, and dynamic/articulated. The primary purpose of both is to safely deliver adequate concentrations of antibiotics over an extended period to the bone and surrounding soft tissues to eradicate the infection ([Figure 5]).

Figure 5 Lateral knee and anteroposterior hip X-rays. Both images show two examples of static or rigid cemented spacers: (a) Static spacer with intramedullary arthrodesis nail that prevents knee flexion-extension. (b) Static hip spacer, a useful option for patients lacking an adductor mechanism in the hip.

Dynamic spacers have certain advantages, such as better preservation of bone stock, less soft tissue retraction, and less muscle atrophy, which contributes to a more favorable functional recovery and facilitates reimplantation surgery ([Figure 6]). Furthermore, they have been observed to reduce hospital stays compared to static spacers. Initially, non-articulating spacers were thought to have lower rates of dislocation and fracture. However, current literature reports similar rates of these complications for both types of spacers, and the latest international consensus tends to favor the use of articulated spacers.[22] [23]

Figure 6 Lateral knee and axial hip X-rays. Articulated spacers offer greater functionality and shorter hospital stays: (a) Mobile knee spacers; continuous movement aids antibiotic diffusion and preserves bone stock. (b) Articulated hip spacer in a case with multiple revision surgeries and significant bone loss.

Currently, spacers can be classified into six major categories[24]:

• · Intraoperatively made spacer, recreating the patient's anatomy or adapting to severe bone defects. They are inexpensive and allow for customized antibiotic loading, but their manufacture is complex and can cause irregularities in the joint surface. ([Figure 7])

• · Silicone or aluminum molds, which allow for the manufacture of more congruent spacers and the customization of the antibiotic load, in addition to facilitating the inclusion of femoral or tibial stems in cases of significant bone defects. ([Figure 6a])

• · Preformed spacers: offer a quick and easy option, although with the disadvantage of not being able to customize the antibiotic load. ([Figure 6b])

• · Prostalac: Hybrid spacers with plastic and metal components coated with antibiotic cement, which improves function between surgical stages without compromising infection eradication.

• · Spacer prosthesis: This uses a sterile prosthesis secured with antibiotic cement. In some studies, up to 40% of patients treated with this technique do not require a second surgery. ([Figure 5a]).

• · Custom-made spacers for massive defects, combining massive prostheses coated with antibiotic cement or reconstruction nails.

Figure 7 AP knee X-ray showing a manually molded spacer. These spacers can be a useful alternative to tailor antibiotics to the specific pathogen and cover large defects in cases of bone stock loss. Clinical image provided by Dr. Almeida F.L.

In addition to improving joint function between surgical stages, antibiotic-loaded cement spacers allow for intra-articular concentrations that exceed the minimum bactericidal concentration, reducing the risk of antibiotic resistance without causing systemic toxicity. To achieve this, the antibiotic used must meet certain criteria: it must be available in sterile powder form, be thermostable and water-soluble, cause minimal inflammatory or allergic reaction in the host, and reach an adequate concentration in the bloodstream without systemic toxicity. The combination of aminoglycosides and glycopeptides, such as gentamicin and vancomycin, is the most used due to their antibiotic synergy and the thermal stability of vancomycin.

Interstage Period

Although it has traditionally been established that a definitive replacement of the components should be delayed at around 6 weeks, the latest revisions are in favor of using acute phase reactants to focus our treatment and not delay the second surgery any longer than necessary ([Figure 8]).

Figure 8 Summary of management strategies for periprosthetic infection. Adapted from Li C. et al.[23]

Thus, for patients who remain asymptomatic, whose PCR has remained negative or within the threshold, and whose soft tissue status is adequate for further surgery, the second approach would be indicated at that time. This new approach reduces unnecessary prolonged hospital stays, prevents the loss of muscle and bone mass, lessens the adverse effects of systemic antibiotic therapy, and allows the patient to rehabilitate more quickly.[25] [26]

On the other hand, there is no evidence that we should leave a period without antibiotic treatment, which is known as an "antibiotic holiday" before the definitive implantation of our prosthesis.[27] The need for culture during reimplantation should not justify observing an antibiotic holiday period, as the data derived from this practice are ineffective in predicting procedural success and guiding the surgical plan. The duration of an antibiotic-free period does not appear to significantly affect the rate of PJI after reimplantation. However, many patients fail during the antibiotic-free period.

Proposed Management Algorithm

The algorithm presented in this paper proposes a structured strategy for the management of periprosthetic infection, based on the time of symptom onset and specific clinical factors. Its application facilitates decision-making between the main therapeutic options: implant-retaining debridement (DAIR) or prosthetic replacement in one or two stages.

The key criteria for each clinical scenario are described below, with examples illustrating their application.

Periprosthetic Infection with Symptoms ≤4-6 weeks

In this group of patients, if the following criteria are met, the DAIR approach is recommended:

• · Absence of fistulas and healthy skin.

• · Identification of the microorganism and confirmed sensitivity to antibiotics.

• · Exclusion of infections with difficult pathogens (polymicrobial, fungal, or enterococcal).

• · Stable implant with no signs of mobilization.

Clinical example:

A 67-year-old male patient with a knee prosthesis implanted 3 months ago presents with pain, mild swelling, and intermittent fever for the past 3 weeks. Joint puncture yields a positive culture for methicillin-sensitive Staphylococcus aureus (MSSA). No fistulas or loosening are observed on the radiograph. In this case, the algorithm indicates the patient is a candidate for DAIR.

If the above criteria are not met, DAIR is ruled out and a prosthetic replacement is considered.

Periprosthetic infection with symptoms >4-6 weeks

In chronic infections, treatment requires a replacement of components, the modality of which will depend on additional clinical factors.

One-stage revision

One-stage revision is considered if the following criteria are met:

• · Microorganisms identified and adequately sensitive to antibiotics.

• · Good bone stock.

• · Good soft tissue condition (no fistulas, well-covered skin).

• · Immunocompetent patient.

• · Absence of sepsis.

Clinical example:

A 72-year-old woman with a hip replacement for 8 years developed an infection with progressive symptoms over the past 3 months. Rifampicin-susceptible Staphylococcus epidermidis was identified by arthrocentesis. There were no signs of fistulas or sepsis, and bone stock was adequate. In this case, a single-stage bone replacement is a viable option.

Two-stage revision

Two-stage revision is preferred in the following scenarios:

• · Infection with microorganisms that are difficult to eradicate (polymicrobial, fungal, enterococcal).

• · Significant bone deficiency.

• · Presence of fistulas or poor skin coverage.

• · Immunocompromised or poorly maintained patient.

• · Presence of sepsis.

Clinical example:

A 74-year-old male with a knee replacement performed 10 years earlier, with a fistula draining purulent material and positive cultures for Enterococcus faecalis and Pseudomonas aeruginosa. He presented with limited bone stock with cortical resorption. In this case, the algorithm indicated the need for a two-stage replacement. Upon surgical revision, abundant sloughing and synovial hypertrophy were observed, and the entire periprosthetic tissue was widely infected ([Figure 9]). After this, it was decided to perform extensive lavage with radical debridement, and the prosthesis was replaced with a preformed cement spacer ([Table 7]). After 6 weeks of antibiotic treatment (intravenous for the first two and oral for the following 4), it was decided to apply a hinge-type prosthesis with a femoral trabecular cone due to the lack of bone stock ([Figure 10] and [11]).

Figure 9 Intraoperative image of a patient requiring a two-stage revision due to knee prosthesis infection. Numerous sloughs covering the knee prosthesis are observed, accompanied by synovial hypertrophy and purulent drainage. Clinical image provided by Dr. López R.

Figure 10 Sequence of X-rays illustrating the two-stage revision process in the same patient: 10a: Initial X-ray showing lateral tibial radiolucency and lytic bone loss in the femur and tibia. 10b: Postoperative X-ray after the first stage with a preformed spacer implant. 10c: X-ray after definitive surgery showing the final hinged prosthesis with tibial and femoral stems. Clinical images provided by Dr. López R.

Figure 11

Conclusions

The management of periprosthetic infections continues to represent a complex clinical challenge, given the variability in their diagnosis and treatment. However, the application of systematic strategies, such as the use of risk stratification scales (e.g., KLIC and CRIME80), allows for more precise guidance in the choice between DAIR and prosthetic replacement in one or two stages. In clinical practice, it is recommended to adopt standardized protocols that include close coordination between multidisciplinary teams - with the participation of specialists in infectious diseases, microbiology, and, when necessary, plastic and reconstructive surgery - to optimize the therapeutic approach.

Furthermore, it is essential to implement measures that facilitate early identification of the microorganism and assessment of the implant's condition, which can significantly improve treatment outcomes. In this context, it is suggested that new diagnostic technologies, such as next-generation sequencing, be integrated to improve decision-making ([Table 8]).

Finally, the development of less invasive surgical techniques and the optimization of antibiotic therapies—especially those targeting biofilm—are key areas for future research. These advances could not only reduce morbidity, mortality, and associated costs but also lay the groundwork for sustained improvements in the management of periprosthetic infections.

Table 7

KLIC Criterion	Patient	Score
Chronic kidney failure (Kidney's disease)	1 points	NO
Cirrhosis (Liver)	1, 5 points	NO
I Index surgery (revision or post-fracture)	1,5 points	NO
C Cementation	2 points	SI
C CPR > 115mg/L	2 points	NO (40)

Table 8

Variable	Score	Patient
C Chronic obstructive pulmonary disease (COPD)	1	SI
CRP > 150 mg/L	1	SI (155)
R Rheumatoid arthritis	3	NO
I Index surgery (following fracture)	3	NO
M Male	1	SI
E Polyethylene exchange	-1	NO
> 80 years	2	SI

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