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Periprosthetic joint infection is a frequent and dreadful complication after total joint arthroplasty. The information they carry is not the same in every clinical scenario, and they should be interpreted accordingly. Serological inflammatory markers have different diagnostic thresholds in acute and chronic situations. Total joint replacement, especially hip and knee, is one of the most successful surgeries in orthopaedics. Periprosthetic joint infection (PJI) is typically classified according to the timing of symptom development and the mechanism of bacterial contamination as acute postoperative, acute delayed (haematogeneous) or chronic. This review confronts the reader with real daily practice doubtful clinical situations and then provides the necessary tools to interpret ESR and CRP values in three different key periods: the immediate postoperative period, diagnosis of a suspected chronic infection and between stages of treatment of an infected total joint arthroplasty. An otherwise healthy 73-year-old man underwent right total knee arthroplasty (TKA) for primary knee osteoarthritis. Nonetheless, after the initial peak, these values should steadily decrease after uncomplicated arthroplasty. Understanding this normal pattern after uncomplicated arthroplasty is the key to better using these inflammatory parameters to our advantage in the diagnosis of early acute PJI. It is therefore crucial to make an accurate and timely diagnosis to increase the chances of success[17]. The increase in ESR and CRP values guided the decision to perform irrigation and debridement of the knee joint in the presented clinical case.
Preoperative identification of PJI in patients presenting with a painful total joint replacement is often difficult. Recently, several studies were undertaken using modern statistical tools known as receiver operator curves. The major finding common to all these studies is that the negative predictive value when both ESR and CRP are under the threshold value is over 95%[19,20,21,22,23].Positive predictive value however, even when both markers are elevated, is not as impressive. Although there is no absolute consensus as to the exact cut-off points of both ESR and CRP, there is enough evidence that they are useful screening tests. A 66-year-old man with a history of right total hip arthroplasty for primary osteoarthritis 3 years ago presented with a painful hip and a chronic draining sinus tract communicating with the prosthesis. First-stage surgery was performed and coagulase-negative Staphylococci grew on several intraoperative samples (Figure 3).
Although numerous studies report favourable outcomes after one-stage revision surgery, two-stage surgery has traditionally been considered as the gold standard for management of chronic infections[24,25].Two-stage exchange consists of debridement, resection of infected implants with or without placement of a temporary antibiotic-impregnated cement spacer and delayed reimplantation of a new prosthesis after infection is deemed to be eradicated.
Determining the appropriate timing and criteria for reimplantation that result in minimal reinfection rates remains controversial.
While reimplanting a new prosthesis in a persistently infected site is a concern, overreliance on normalization of these serological markers may lead to an exaggerated and unnecessary time interval between stages, thus increasing patient morbidity.
The decision regarding the exact timing for reimplantation remains difficult as it relies for the most part on the subjective clinical judgement of the treating physician. The authors believe there is little role for deferring reimplantation until all serologic markers have normalized. Several other serological markers have been studied in the context of prosthetic joint infection. These alternatives are neither as extensively studied nor as widely available as ESR and CRP. All authors contributed to conception and design, manuscript preparation, read and approved the final manuscript.
Serological inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are widely available and easy to use. This review confronts the reader with different doubtful clinical situations and then provides the necessary tools to interpret ESR and CRP in each of them: the immediate postoperative period, the chronic painful arthroplasty and between two-staged revision of infected cases. Follow-up measurements during treatment are informative, but complete normalization is not a mandatory requirement for successful outcome. The demand for total hip and knee joint arthroplasty is increasing and is expected to grow even further over the coming decades[1]. As such, preoperative diagnosis is forced to rely on clinical suspicion as well as on careful scrutiny of laboratory and imaging modalities[7]. The first few days after the procedure were uneventful and the patient was discharged on the fifth postoperative day. It is a non-specific haematological test routinely used as an indirect measure of inflammation.
The peak is significantly higher after TKA in comparison with THA because the bone and soft tissue trauma is higher in TKA[8,9]. ESR levels usually peak on the fifth postoperative day and drop close to preoperative levels by the end of the third month after THA and the ninth month after TKA[8,11].

Although recent reports have questioned the real value of irrigation and debridement as a means to achieve eradication of infection under specific circumstances[16], it is still widely recommended in acute postoperative infections especially in the first 3–4 weeks after surgery[17]. Intraoperative microbiology samples confirmed a polymicrobial infection by methicillin-sensitive Staphylococcus aureus and Enterobacter clocae.
Given their wide availability, ESR and CRP are often used as initial tests even when there is a low suspicion of PJI[6]. A meta-analysis by Berbari et al.[19] shows that ESR sensitivity and specificity is 75% and 70% respectively and CRP has a slightly higher accuracy, reaching 88% sensitivity and 74% specificity. The goal is to optimize these classic threshold values, thus providing higher sensitivity and specificity for the diagnosis of PJI. After 2 weeks of IV antibiotics, the patient was discharged and sent home with oral antibiotics for another 4 weeks. Most surgeons prefer that ESR and CRP return to normal before proceeding with reimplantation, but there really is no solid scientific evidence to back it up[26,27].Some investigators have proceeded with reimplantation only when knee aspirate cultures were negative for bacterial growth, but the high false-negative rates of culture possibly resulting from the prolonged antibiotic treatment raise concerns[28,29]. Favourable local soft tissues, such as correct wound healing and absence of local warmth, are a major factor. In the case presented, good local soft tissue conditions guided the decision to go ahead with second-stage surgery despite persistent elevation of inflammatory parameters. Procalcitonin has been studied especially in the diagnosis of infection in the chronic setting. The latter are simple routine laboratory tests performed worldwide that can give precious and due time information in a variety of clinical scenarios regarding prosthetic joint infections. Nevertheless, the information they provide is not the same in every clinical scenario and they should thus be interpreted accordingly.
As such, they are often used as preliminary diagnostic as well as follow-up tools during the course of treatment.
Infection is arguably the most challenging and certainly one of the most frequent complications after joint replacement[2,3].
Timely recognition of this grievous complication is crucial as it may make the difference between successful and failed outcome. In this setting, serological inflammatory markers, specifically erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), are often used as initial tests even when there is a low suspicion of PJI[6]. Due to the very high interindividual variations of these values, it is not possible to find a threshold that predicts the presence of infection[10].
This simple procedure entails reopening the joint through the original incision, removal of unhealthy tissues, thorough lavage and exchange of modular components, while retaining fixed components. A red and swollen joint or even superficial inflammatory signs are not always indicative of infection in the early postoperative period. Appropriate antibiotic therapy was given after surgery, and 2 years after the surgery, the patient remains free of infection.
The first few postoperative weeks were uneventful, but a relentless pain had been bothering her ever since. They also found that the diagnostic odds ratio was higher for TKA than for total hip arthroplasty for all markers. In their study including 109 infected total knee replacements treated according to the two-stage protocol, 23 patients (21%) required revision surgery for recurrence of prosthetic joint infection. In this regard, the knee being a more superficial joint than the hip, allows an easier and more trustworthy clinical assessment.
Although it has been shown to have a good specificity (albeit not higher than CRP), it has a low sensitivity and a negative predictive value[32].
Diagnostic thresholds are different in the acute and chronic infected prosthetic joints and possibly also different between hip and knee replacements. Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. Despite modern surgical prophylaxis, the incidence of this complication is rising worldwide[4,5]. They are also commonly used in monitoring response to therapy since they are inexpensive, non-invasive and widely available tests. On the 18th postoperative day, the patient presented to the outpatient clinic with scarce serous wound drainage through a small area of macerated-looking skin wound. To understand the importance of these markers in the postoperative period, it is essential to know their normal kinetic patterns after uncomplicated arthroplasty. Scarce serous wound drainage may be normal but, if persistent, it is a known risk factor for infection. If at least one of them is positive, a subsequent confirmatory evaluation should be undertaken[6]. Increasing diagnostic thresholds values to increase specificity should be interpreted with caution to avoid significantly lowering the negative predictive value (i.e.

There were no significant differences in mean ESR or CRP values (at the time of reimplantation) or significantly different variations of these parameters (between resection and reimplantation) when comparing both groups. Favourable ESR and CRP kinetics, especially after antibiotic discontinuation, serve as an adjunct to decision, but complete normalization is neither essential nor enough to ensure a successful outcome.
Follow-up measurements during treatment are somewhat informative, but complete normalization is not a mandatory requirement for successful outcome. It is therefore likely that an increasing number of orthopaedic surgeons and other clinicians will encounter this problem.
It rises more rapidly, usually peaking on the second or third day and falls swiftly by the fifth to seventh day[11,14,15].
Maathuis et al.[18] proposed a protocol using ESR and CRP as an adjunct to clinical judgement to help dictate the need and timing for debridement in patients with persistent drainage after total joint replacement.
These findings were later confirmed by an independent study group that studied serum ESR and CRP as well as synovial fluid white blood cell count and differential before the second stage[31].
Return to normal values occurs approximately by the third week after THA, and it may take up to 2 months after TKA[8,12,13]. Serial measurements of these inflammatory parameters were taken in suspicious circumstances, and only a decrease in ESR and CRP or a decrease in drainage could postpone or alter the decision to perform open debridement. The authors were unable to identify any single, or combination of, commonly used testing modalities to reliably identify persistent infection following resection TKA for a deep periprosthetic infection.
Small and seemingly superficial area of skin necrosis was present, and there was no drainage or obvious inflammatory signs (Figure 1). The ESR and CRP were particularly unreliable and frequently abnormal even when the infection had been controlled.
The much faster peak and return to normal can hypothetically be advantageous and allow an earlier diagnosis[34]. As the expected return to normal after uncomplicated arthroplasty is faster, an infection can be hypothetically detected by an earlier increase in IL-6 levels than in CRP levels.
New definition for periprosthetic joint infection: from the Workgroup of the Musculoskeletal Infection Society. C-reactive protein values and erythrocyte sedimentation rates after total hip and total knee arthroplasty. Postoperative physiopathological analysis of inflammatory parameters in patients undergoing hip or knee arthroplasty. Changes in erythrocyte sedimentation rate and C-reactive protein after total hip arthroplasty. Erythrocyte sedimentation rate and C-reactive protein values in patients with total hip arthroplasty. Diagnosis and management of prosthetic joint infection: clinical practice guidelines by the infectious diseases society of america. Timing of open debridement for suspected infection of joint prosthesis: a report on 551 patients. Inflammatory blood laboratory levels as markers of prosthetic joint infection: a systematic review and meta-analysis.
Use of erythrocyte sedimentation rate and C-reactive protein level to diagnose infection before revision total knee arthroplasty. The use of receiver operating characteristics analysis in determining erythrocyte sedimentation rate and C-reactive protein levels in diagnosing periprosthetic infection prior to revision total hip arthroplasty. Efficacy of erythrocyte sedimentation rate and C-reactive protein level in determining periprosthetic hip infections.
Evaluation of preoperative cultures before second-stage reimplantation of a total knee prosthesis complicated by infection. Staged revision for knee arthroplasty infection: what is the role of serologic tests before reimplantation? What is the role of serological testing between stages of two-stage reconstruction of the infected prosthetic knee?. Interleukin-6, procalcitonin and TNF-alpha: markers of peri-prosthetic infection following total joint replacement. Serum interleukin-6 as a marker of periprosthetic infection following total hip and knee arthroplasty.

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