
==== Front
BMC Musculoskelet Disord
BMC Musculoskelet Disord
BMC Musculoskeletal Disorders
1471-2474
BioMed Central London

7840
10.1186/s12891-024-07840-0
Research
The presence of a sinus tract is associated with reinfection after two-stage revision surgery for prosthetic hip joint infection: a case-control study
Xu Hongjun
Li Songlin
Liu Sen
Li Shanni
Yin Zhaojing
Du Yiyang
Weng Xisheng
Qian Wenwei qianww007@163.com

grid.413106.1 0000 0000 9889 6335 Department of Orthopedic Surgery, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, 100730 China
7 9 2024
7 9 2024
2024
25 7212 3 2024
30 8 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Background

Reinfection rates after two-stage revision (TSR) for prosthetic joint infection (PJI) range from 7.9 to 14%. Many factors, including sinus tracts, are associated with reinfection after this procedure. This study aimed to delineate whether the presence of sinus tract could increase reinfection rate after TSR and to investigate other potential risk factors for reinfection after TSR.

Methods

We conducted a case-control study by retrospectively reviewing patients who underwent TSR for prosthetic hip joint infection from 2002 to 2022. The case group included patients who developed reinfection after TSR, while the control group consisted of patients who did not experience reinfection. PJI and reinfection after TSR were defined based on Delphi-based international consensus criteria. Patient demographics, past medical history, clinical manifestations, laboratory results, interval between stages, microbiological culture results were collected. Univariate analyses were utilized to assess the effect of sinus tract on reinfection and to identify other risk factors for reinfection after TSR.

Results

Six patients with reinfection after TSR were included as the case group and 32 patients without reinfection were in the control group. Significant difference was observed in percentage of patients with sinus tracts between the two groups (67% in the case group versus 19% in the control group, p = 0.031, OR = 8.7). Significant difference was also found in percentage of patients with positive cultures of synovial fluid and synovium harvested during the first-stage revision between the two groups (100% in the case group versus 50% in the control group, p = 0.030). Additionally, patients in the case group had a significantly higher C-reactive protein (CRP) level prior to the second stage revision than that of patients in the control group (8.80 mg/L versus 2.36 mg/L, p = 0.005), despite normal CRP levels in all patients.

Conclusions

Our study revealed that the presence of sinus tracts could significantly increase risk of postoperative reinfection after TSR. Positive cultures during the first stage revision and elevated CRP level prior to the second stage revision could also increase the risk of reinfection after TSR. Further studies with a larger sample size are required.

Trial registration

Retrospectively registered.

Keywords

Periprosthetic joint infection
Two-stage revision
Hip
Sinus tract
Reinfection
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pmcIntroduction

Prosthetic joint infection (PJI), defined as infection involved the joint prosthesis and adjacent tissue, is one of the most devastating complications after arthroplasties. PJI can cause joint pain, fever, prothesis loosening, joint dysfunction and expose patients to risk of multiple surgeries, increasing economic cost and mortality rate [1, 2]. PJI after total hip arthroplasty ranges from 0.8 to 2.1%, accounting for 14.8% revisions of prosthetic hip joint [3–5]. The International Consensus on Orthopedic Infections definition (2018) with 2 major criteria and 7 minor criteria is commonly used for the diagnosis of PJI [6]. Anemia, malnutrition, obesity, history of intra-articular injection within 3 months, prolonged operation time, and wound healing complications are all risk factors for PJI [7–10]. The most common pathogens in PJI is coagulase-negative staphylococci (especially Staphylococcus epidermidis), followed by Staphylococcus aureus, streptococcus species, enterococcus species, cutibacterium species, and Enterobacterales [11]. As main materials of joint prothesis, titanium (and its alloys), cobalt-chromium, various polymeric biomaterials (e.g. ceramics, hydroxyapatite, and polyethylene), and polymethylmethacrylate (PMMA) are susceptible to adhesion and colonization by biofilm-forming bacteria [12]. Besides, the rough surface of the prosthesis is also more likely to lead to bacterial adhesion [13].

PJI is challenging for orthopedists to treat due to the potential of reinfection and bone loss. For patients of acute PJI without sinus tracts and loose prothesis, debridement, antibiotics, and implant retention (DAIR) is the treatment of choice [14, 15]. For chronic PJI, patients are often offered a one-stage or two-stage revision. One-stage revision (removal of the infected prothesis and reimplantation of a new prothesis during one procedure) is alternative for patients with intact or only slightly compromised bone and soft tissue [2]. While two-stage revision (TSR) is usually considered as the gold standard of treatment for PJI [16]. TSR consists of two separate surgeries: the first stage is to remove all the implants followed by a complete debridement of abnormal tissues and thorough irrigation. After that, an antibiotic-loaded spacer, often comprised of polymethylmethacrylate (PMMA), is inserted. Spacers can be articulated or nonarticulated, and can be prefabricated or surgeon made [17, 18]. During the interval, around 16–18% patients might experience spacer exchange due to recalcitrant PJI [19]. After six weeks of systemic antibiotic therapy and two to eight weeks of antibiotic-free period, the spacer is removed and followed by debridement and irrigation. Then, the prosthesis is reimplanted [16]. A period of total 6–8 week interval was commonly used before removing the spacer, while the optimal timing to remove the spacer and reimplant the prothesis has not yet been defined [20, 21].

Unfortunately, reported rate of reinfection after TSR still remained 7.9 -14% [22, 23].Little is known about the risk factors for the recurrence of PJI after TSR, although several studies have been conducted [24–30]. For instance, the literatures reported that the presence of a sinus tract was an independent risk factor for recurrent infection of two-stage revision total knee arthroplasty and the first stage of TSR [31, 32]. While these studies did not report the impact of a sinus tract on the failure of two-stage revision total hip arthroplasty.

Here, we conducted a case-control study to (1) primarily investigate whether the presence of a sinus tract is associated with reinfection after TSR for prosthetic hip joint infection, and (2) secondarily to explore positive rate of microbiological cultures and risk factors associated with reinfection. We hypothesized that the presence of a sinus tract could increase reinfection rate after TSR for PJI of hip.

Materials and methods

Patients

We retrospectively reviewed medical records of patients who underwent TSR for prosthetic joint infection (PJI) of the hip at a single medical center from 1 January, 2002, to 31 December, 2022 (Fig. 1). When reviewing the medical record, the diagnosis of PJI was reaffirmed using Delphi-based international consensus criteria by a 3th and 4th-year orthopedic resident, each of whom systematically learned this consensus at the start of the study (Fig. 2) [6]. Any discrepancy was resolved through consultation with a senior orthopedic surgeon with at least 20 years of experience. Patients (aged ≥ 18 years) diagnosed with reinfection of prosthetic hip joint after the second stage revision were included as the case group. Reinfection of prosthetic hip joint was defined according to Delphi-based international consensus criteria. The exclusion criteria were the following: (1) patients without complete medical records; (2) patients who received the first or second stage revision of prosthetic hip at another hospital; (3) patients who received two-stage revision for reasons other than PJI. The control group contained patients without recurrence of prosthetic joint infection of the hip after the second stage revisions of prosthetic hips. No recurrence of prosthetic joint infection was defined as no clinical or laboratory evidence of hip infection and no signs of prosthetic loosening. Clinical evidence includes presence of sinus tract and pain in the affected joint. Laboratory evidence of reinfection includes elevation of serum C-reactive protein (CRP), D-dimer and erythrocyte sedimentation rate (ESR).

Fig. 1 Flowchart of patient selection process

Fig. 2 Delphi-based international consensus criteria

During the first-stage revision, a handmade articulating spacer composed of bone cement and vancomycin was inserted in all patients [17]. After the first stage, systemic anti-infection therapy was administered according to antimicrobial susceptibility tests. Patients were given antibiotics intravenously for two weeks during hospitalization and oral antibiotics for four weeks after discharge. Patients with negative cultures were given vancomycin and meropenem intravenously for two weeks during hospitalization and sulfamethoxazole and linezolid orally after discharge for another four weeks. Antibiotic therapy was performed for totally more than six consecutive weeks until normalization of white blood cell (WBC) count, CRP and ESR. Then, more than two weeks of antibiotic holiday period followed until the second-stage revision was performed.

Data collection

Patients’ medical records during hospitalization were reviewed to collect the demographic characteristics, past medical history, operation information, laboratory test results, clinical manifestations, and any complications related with revision surgeries. Clinical manifestations including arthralgia, joint swelling, the presence of sinus tract, body temperature. Other related information, such as range of motion, change of body temperature after TSR, was collected by interviewing patients or their family members. Patients’ age, gender, body weight, body mass index (BMI), history of diabetes mellitus, history of rheumatic diseases, history of smoking, and American Society of Anesthesiologists score (ASA score) were collected as the demographic characteristics. History of rheumatic diseases was defined as the presence of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), Sjogren’s syndrome, and antiphospholipid syndrome. The interval between the first stage revision and the second stage revision, and the history of previous surgery, infection and intraarticular injections of the affected hip joint were also abstracted and analyzed as potential risk factors. Laboratory test results included serumCRP level, WBC count, ESR and D-dimer level prior to the second-stage revision, and organism cultures during the first-stage revision. All of data were collected by two doctors separately. The primary endpoint was the difference in sinus incidence between the two groups. The secondary endpoints were differences in microbial culture positive rates, CRP levels, ESR levels, and D-dimer levels between the two groups.

Statement of human and animal rights

Ethics approval from the Institutional Review Board (No. K5245) was obtained. The clinical investigation was conducted according to the principles of the Declaration of Helsinki.

Statistical analyses

All data analyses were performed using Statistical Package for the Social Sciences (SPSS) 25.0 for windows (SPSS institute, Chicago, IL, USA). For continuous variables, Shapiro-Wilk test was used to evaluate the normality of the distribution of each parameter. Continuous variables with normal distribution were described as mean ± standard deviation (SD), and the unpaired t-test was used to assess differences between the case group and the control group in these variables. While those with non-normal distribution were presented as median and interquartile range (IQR), and the Mann-Whitney test was used. Categorical variables were described as absolute value and percentages. Comparisons of categorical variables were performed by using Fisher exact test. p value < 0.05 was considered statistically significant.

Results

Demographic characteristics

38 patients who received two-stage revision for prosthetic hip joint infection were screened. Prior to intraarticular fluid aspiration for cytology analysis, all patients had received empiric antibiotic therapy before being transferred to our institution. The mean follow-up of the control group was 55 months (range, 19–126 months). Within these 38 patients, six patients, constituting the case group, were diagnosed with reinfection of hip joint subsequent to two-stage revision. The remaining 32 patients, who had no reinfection of prosthetic hip joint, constituted the control group. The demographic characteristics comparison between the case group and the control group is shown in Table 1. The case group comprised three females (50%) and three males (50%) with an average age at the time of TSR of 58 ± 12 years. While in the control group, the number of females and males was 14 (44%) and 18 (56%) respectively (p = 0.746). And the average age at the time of TSR was 56 ± 16 years in the control group (p = 0.999). Average body weight was 69 ± 22 kg in the case group and 66 ± 11 kg in the control group (p = 0.685). As for average body mass index (BMI), it was 24.60 ± 5.03 kg/m2 in the case group and 23.43 ± 3.31 kg/m2 in the control group (p = 0.469). The number of patients with their American society of Anesthesiologists scores (ASA scores) surpassing 2 was three (50%) in the case group and eight (25%) in the control group, with no statistically significant difference observed (p = 0.329). In the case group, the prevalence of diabetes mellitus was observed in three patients (50%), comparing with four patients (13%) in the control group (p = 0.063). Three out of six patients (50%) in the case group had a history of rheumatic diseases—one with systemic lupus erythematosus (SLE) (17%), one with rheumatoid arthritis (RA) (17%), and another with ankylosing spondylitis (AS) (17%). In the control group, seven out of 22 patients (33%) had a history of rheumatic diseases, in which one patient had RA (5%), five patients had SLE (23%), and one patient had antiphospholipid syndrome (APS) (5%). Comparisons of the incidence of rheumatic disease between the two groups showed no significant difference (p = 0.310), either. Additionally, compared with six patients (19%) in the control group, the number of patients with a history of smoking was one (17%) in the case group without statistical difference being found (p = 0.999). In the control group, one patient had a history of core-decompression of the affected hip, and one patient had a history of internal fixation for a fracture of the femoral neck on his affected hip. In the case group, none of the patients had a history of surgery on the affected hip. No patient in either group had received intraarticular injections of the hip.

Table 1 Demographic characteristics

	Total	reinfection	no reinfection	p-value	
Patients (n)	38	6	32	-	
Female sex (n[%])	17 (45)	3 (50)	14 (44)	0.999	
Age (years)	56 ± 15	58 ± 12	56 ± 16	0.746	
Body weight (kg)	66 ± 12	69 ± 22	66 ± 11	0.685	
BMI (kg/m2)	23.61 ± 3.57	24.60 ± 5.03	23.43 ± 3.31	0.469	
ASA ≥ 3 (n[%])	11 (29)	3 (50)	8 (25)	0.329	
History of Diabetes (n[%])	7 (18)	3 (50)	4 (13)	0.063	
History of Rheumatic disease (n[%])	10 (26)	3 (50)	7 (22)	0.310	
History of Smoking (n[%])	7 (18)	1 (17)	6 (19)	0.999	
BMI: body mass index

ASA: American Society of Anesthesiologists

Clinical findings

Prior to the first stage revision, four patients in the case group had sinus tracts around their prosthetic hip joints (67%). While in the control group, six patients had sinus tracts, which only accounted for 19% of the group. Significant difference was found between these two groups (p = 0.031). We also calculated by odds ratio (OR) the impact that the presence of sinus tract has, as a risk factor, in the reinfection after TSR. A value of OR of 8.7 was revealed. Duration of interval between the first stage revision and the second stage revision was 5 (3–12) months in the case group, while in the control group, it was 7 (5–11) months (p = 0.245).

As for laboratory results, average albumin level in the case group was 36 ± 6 g/L, which was the same as that in the control group (p = 0.819). Average lymphocyte count was 1.60 ± 0.42 × 109/L in the case group and 1.78 ± 0.51 × 109/L in the control group (p = 0.424). Inflammatory indices were collected before the second stage revision, including serum C-reactive protein (CRP) level, white blood cell (WBC) count, erythrocyte sedimentation rate (ESR) and D-dimer level. Average WBC count was 7.20 ± 2.28 × 109/L in the case group and 5.97 ± 1.46 × 109/L in the control group, which showed no significant difference (p = 0.093). The case group had a significantly higher CRP level than that of the control group (8.80 (5.68–16.18) mg/L vs. 2.36 (1.10–5.6) mg/L; p = 0.005). Median ESR in the case group was 21 (12–37) mm/H and in the control group, it was 14 (5–25) mm/H (p = 0.159). As for D-dimer, median level of D-dimer in the case group was 1.11 (0.55–1.46) mg/L, and in the control group, it was 0.81 (0.52–1.19) mg/L, with no significance being found (Table 2).

Table 2 Univariate analysis

	Total	reinfection	no reinfection	p-value	
Presence of sinus tract (n[%])	10 (26)	4 (67)	6 (19)	0.031	
Positive cultures (n[%])	21 (55)	6 (100)	15 (47)	0.024	
Interval (months)	7 (5–10)	5 (3–12)	7 (5–11)	0.245	
Albumin (g/L)	36 ± 4	36 ± 6	36 ± 4	0.819	
LY (×109/L)	1.75 ± 0.49	1.60 ± 0.42	1.78 ± 0.51	0.424	
WBC (×109/L)	6.16 ± 1.64	7.20 ± 2.28	5.97 ± 1.46	0.093	
D-dimer (mg/L)	0.83 (0.55–1.22)	1.11 (0.55–1.46)	0.81 (0.52–1.19)	0.469	
ESR (mm/H)	14 (6–27)	21 (12–37)	14 (5–25)	0.159	
CRP (mg/L)	2.92 (1.29–7.40)	8.80 (5.68–16.18)	2.36 (1.10–5.6)	0.005	
LY: Lymphocyte

WBC: White blood cell

ESR: erythrocyte sedimentation rate

CRP: C-reactive protein

As for complication related with TSR, one patient in the control group sustained dislocation on the sixth postoperative day, and a closed reduction was then performed. No aseptic loosening, spacer fracture or pulmonary embolism was observed in our study.

Microbiological findings

Samples from synovial fluid and synovium were harvested for bacteria culturing during the first stage revision. In the case group, 6 patients had positive results of microbiological cultures, accounting for 100%. Among them, 3 (50%) patients had positive cultures of staphylococcus aureus, 2 (33%) patients for methicillin resistant staphylococcus epidermidis (MRSE), and 1 (17%) patient for Proteus mirabilis. In the control group, 16 patients had positive results of bacteria cultures, accounting for 50%. Among these 16 patients, 2 (13%) patient had positive culture of staphylococcus aureus, 4 (27%) patients for MRSE, 2 (13%) patients for methicillin resistant staphylococcus aureus (MRSA), 2 (13%) patients for methicillin resistant staphylococcus coagulase negative (MRSCON), 1 (7%) patient for Escherichia coli., 1 (7%) patient for Enterobacter cloacae., 2 (13%) patients for Salmonella typhimurium, 1 (7%) patient for Klebsiella pneumoniae, and 1 (7%) patient for Acinetobacter pittii. Comparisons of the number of positive cultures between the two groups was significantly different (p = 0.030) (Table 3).

Table 3 Microbiological findings

Pathogen	Reinfection	No reinfection	
Gram +	5		10		
	MSSA	3	MSSA	2	
	MRSE	2	MRSE	4	
			MRSA	2	
			MRSCON	2	
Gram -	1		6		
	Proteus mirabilis	1	Escherichia coli	1	
			Enterobacter cloacae	1	
			Salmonella typhimurium	1	
			Klebsiella pneumoniae	2	
			Acinetobacter pittii	1	
Gram +: Gram-positive bacteria

Gram –: Gram-negative bacteria

MSSA: methicillin sensitive staphylococcus aureus

MRSE: methicillin resistant staphylococcus epidermidis

MRSA: methicillin resistant staphylococcus aureus

MRSCON: methicillin resistant staphylococcus coagulase negative

Discussion

Our study compared demographic characteristics, potential risk factors and microbiological characteristics between the reinfection group and the non-reinfection group, finding that patients with the presence of sinus tracts (p = 0.031) and positive cultures of synovial fluid and synovium harvested during the first-stage revision (p = 0.030) could significantly increase reinfection rate after TSR. Furthermore, the reinfection group exhibited a higher CRP level than that of the non-reinfection group, although all patients had normal CRP levels.

Diabetes mellitus was considered as the risk factor for PJI after the first-time THA [33]. In another study, HbA1c levels ≥ 7% prior to the second-stage surgery was also identified as a risk factor for reinfection [34]. In our study, the case group showed higher rate of patients with diabetes mellitus (50% in the case group versus 13% in the control group), although this difference did not reach statistical significance (p = 0.063). However, the p-value approached 0.05, the predetermined threshold. Besides, the duration of diabetes mellitus and the level of blood sugar in the two groups were not collected and compared, potentially confounding its effect.

Rheumatic diseases could elevate risk for PJI after total joint arthroplasty due to alterations in the immune system induced by the disease itself and use of disease-modifying antirheumatic drugs (DMARD) [35–37]. The present study showed a higher incidence of patients with concomitant rheumatic diseases compared to the control group, while this difference was not significant (50% in the case group vs. 22% in the control group, p = 0.310). We supposed that patients diagnosed with prosthetic hip joint infection may inherently have a heightened prevalence of rheumatic diseases, complicating the detection of significant difference between the case group and the control group, especially when the sample size was relatively small. Furthermore, duration of rheumatic diseases, and specific dosage and type of DMARD administered to patients were not recorded in detail, which might hinder the effect that rheumatic diseases produced.

Sinus tract, defined as a draining tract extending from the infectious joint interior to the skin surface exterior, plays an important role in the diagnosis of prosthetic joint infection. Alexandra et al. conducted a retrospective study of 240 patients (including 170 knees and 70 hips) treated for PJI with intended two-stage revision trying to explore the effect of the presence of sinus tract [38]. They found that patients with sinus tracts were significantly less likely to be re-implanted compared to those without a sinus tract at presentation. But difference of the rate of reinfection between the sinus tract group and no sinus tract group was not significant. However, opposite results were shown in a retrospective cohort study conducted by Wang et al., in which researchers found that presence of sinus tract before treatment was an independent risk factor for reinfection after the first stage revision [32]. In our study, four patients had sinus tracts before TSR in the case group, accounting for 67%, while six patients had sinus tracts in the control group, accounting for 19%. A value of OR of 8.7 was calculated. Significant difference was found, indicating that presence of sinus tract before surgery can increase the risk of reinfection after TSR. We inferred that the presence of a sinus tract reflected the intensity of local inflammatory reactions and extent of infection within the local joint, which impacted the ability of local tissues to manage infection and undergo healing. Therefore, more attention should be paid to the patients with a sinus tract when TSR is intended to be performed. Additionally, during the first-stage revision surgery, it is necessary to thoroughly remove the sinus tract as well as any suspiciously infected or affected soft tissues surrounding the sinus tract.

The optimal duration of interval between the first and second stage revision in PJI has not yet been defined. T Winkler et al. conducted a prospective study wherein they defined a short interval as less than 4 weeks and a long interval as equal to or longer than 4 weeks. Their findings indicated that the outcomes of two-stage revision with a long interval were comparable to those of TSR with a short interval [21]. Similarly, in a meta-analysis performed by J Puetzler, compared with the long interval group, similar or even better infection control was observed for short interval [25]. However, existing literatures had a relatively small sample size, and the definitions of long interval and short interval lack consistency. In our study, the duration of interval in the case group was not significantly different from that of the control group, which was in line with previous studies. It was deduced that an interval less than 4 weeks could provide advantages treating PJI, such as reducing immobilization time and lowering economic costs. Apart from the rate of reinfection, inter-stage mortality is another important factor that we must take into consideration when determining the optimal time for reimplantation. Molly A Hartzler et al. reported a 3% mortality rate and a 28% complication rate between stages [39]. Keith R Berend also reported a 7% inter-stage mortality rate among patients with prosthetic hip joint infection [40]. It was inferred that a reduction of duration of interval was highly likely to reduce the rate of complications and mortality caused by long-term immobility [21]. However, due to concerns about infection control and inability to determine the exact time for reimplantation, some doctors avoided shortening duration of the interval and sometimes repeated the first-stage debridement.

Laboratory results, including serum CRP level, ESR and D-dimer level, serve as important reference indicators for surgeons to decide the timing to reimplantation. However, there is no standard in terms of laboratory results, with which surgeons can identify the patients who are at high risk of reinfection after TSR. Recently, Christian Klemt et al. conducted a study for exploring the role of CRP level and ESR prior to the second stage revision for knee in predicting optimal timing to reimplantation [41]. Results showed that patients with the elevated ESR and CRP level had a significantly higher reinfection rate than patients with normalized ESR and CRP, patients with elevated ESR and normalized CRP, and patients with normalized ESR and elevated CRP. These results indicated that elevation of both ESR and CRP were associated with a higher risk of reinfection compared with normalized either ESR or CRP. In our study, results showed that patients with diagnosis of reinfection after TSR had significantly higher median CRP level prior to the second stage revision compared with patients without reinfection (8.80 mg/L versus 2.36 mg/L, p = 0.005), even though all patients’ CRP level were normalized, which were partially in line with the study of Christian Klemt et al. Therefore, patients with normalized CRP level prior to the second stage revision, which was defined with the present cut-off value, are still possibly at high risk of reinfection after TSR. However, another three studies exhibited conclusions that CRP, serum WBC count and ESR were not helpful to decide the timing of reimplantation and could not predict reinfection after TSR, which were contrary to ours [27, 29, 30]. Nevertheless, two of these three studies included both patients underwent TSR of hip and patients underwent TSR of knee [27, 29]. While in the other study, there was no antibiotics holiday period for patients between the two stages, and thus CRP level and WBC count might not return to the state prior to PJI after six-week anti-infection therapy [30]. All the same, we should still keep in mind that when determining the timing to perform the reimplantation, we ought to consider other inflammatory indices, patients’ clinical signs and the course of antibiotics as well, rather than rely on a specific index. For patients with sinus tracts, during the antibiotics-free period, it is essential to actively monitor CRP levels and their trends. Besides, further research is needed to provide more proofs for the predictive power of CRP level on reinfection and define the new cut-off value for predicting reinfection.

Gram-positive cocci accounts for the majority of PJI with monomicrobial infections [2]. Likewise, our study also showed that gram-positive cocci were detected in 15 patients out of 22 patients who had positive cultures before the first-stage revision. However, positive culture rate in our study was only 58%, which was lower than other studies [42]. It was probably because samples for culturing were obtained from synovial fluid and synovium during the first-stage revision, before which systemic antibiotics had already been administered for a period. Prior studies indicated that culture-negative and culture-positive PJIs had a similar reinfection rate after TSR, which were different from our study [43, 44]. In our study, results showed that the reinfection group had a higher percentage of positive cultures when compared with the no-reinfection group (100% versus 50%, p = 0.030), indicating that positive culture during the first-stage revision was a risk factor of reinfection after TSR for prosthetic hip joint infection. We proposed that patients with negative cultures were more likely to achieve infection control due to their good immunity and the lower toxicity of the bacteria they might be infected with. Thus, these patients might have a lower reinfection rate. In addition, even though we did not detect any patients with polymicrobial infections in our study, it was reported by some authors that polymicrobial infections were associated with failure of TSR [45, 46]. Moreover, among patients with positive cultures, three of six patients in the reinfection group were infected with Methicillin Sensitive Staphylococcus Aureus (MSSA) (50%), while in the no-reinfection group, there were only two of 16 patients infected with MSSA (25%). In line with our results, Curtis W Hartman et al. also reported a statistically significant association between infection with MSSA and reinfection (P = 0.046) [47]. As for post-operative antibiotic therapy, the combination of vancomycin and meropenem were administered intravenous for two weeks for culture-negative PJIs during the stay in the hospital. Discharged patients continued the combination of sulfamethoxazole and linezolid orally another four weeks. In our study, culture-negative patients had no reinfection during the follow up, thus we believe this regimen can treat almost all the microbial organisms except for tuberculosis and fungi.

Finally, there are some limitations in our study that should be taken into consideration when interpreting the results. First, this is a retrospective case-control study with inherent limitations. Second, due to a relatively small sample size, regression analysis could not be performed. Third, patients without complete medical records and patients who received the first-stage or the second-stage revision at other hospitals were excluded, which might lead to incomplete inclusion of the cases without reinfection after TSR. Therefore, in the future, we will try to conduct a multi-center, prospective study with larger sample sizes to further investigate these risk factors.

Conclusions

In conclusion, thiswe presented a case-control study showed that the presence of sinus tracts around the prosthetic hip joint prior to the first-stage revision could significantly increase risk of postoperative reinfection. Additionally, positive cultures of synovial fluid and synovium during the first stage revision and elevated CRP level prior to the second stage revision could also significantly increase the risk of reinfection after TSR for PJI of hip. Further studies with a larger sample size are required to confirm these findings and develop effective prevention.

Acknowledgements

Not applicable.

Author contributions

All authors contributed to the study design. Material preparation, data collection and analysis were performed by Hongjun Xu, Songlin Li, Sen Liu. The first draft of the manuscript was written by Hongju Xu, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Funding

This work was supported by the National High Level Hospital Clinical Research Funding (Grant number: 2022-PUMCH-B-001) and the CAMS Innovation Fund for Medical Sciences (CIFMS, 2022-I2M-C&T-B-034).

Data availability

Raw data and materials of this study is kept in the local server of Peking Union Medical College Hospital for the purpose of safety and confidentiality. Our data are available upon request for non-commercial research purpose.

Declarations

Ethics approval and consent to participate

Ethics approval was granted by the Ethics Committee of Peking Union Medical College Hospital (No. K5245). Written informed consents were obtained from patients who were literate. While for patients who were illiterate or could sign their names, verbal informed consents from the patients and written informed consents from the patients’ guardian were acquired. This study was performed in line with the principles of the Declaration of Helsinki.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Abbreviations

TSR Two-stage revision

PJI Prosthetic joint infection

CRP C-reactive protein

ESR Erythrocyte sedimentation rate

WBC White blood cell

MRSE Methicillin resistant staphylococcus epidermidis

MRSA Methicillin resistant staphylococcus aureus

MRSCON Methicillin resistant staphylococcus coagulase negative

BMI Body mass index

ASA American Society of Anesthesiologists

DMARD Disease-modifying antirheumatic drugs

SLE Systemic lupus erythematosus

RA Rheumatoid arthritis

AS Ankylosing spondylitis

LE Leukocyte esterase

PMN Polymorphonuclear percentage

LY Lymphocytes count

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References

1. Yoo SJ, Rho YH, Nam KW et al. Letter to Editor Concerning Total Hip Arthroplasty Using Ceramic-on-ceramic Bearing Surfaces: Long-term Assessment of Squeaking Sounds by Kim. (Hip Pelvis. 2018;30(1):18–22, 10.5371/hp.2018.30.1.18.) Hip Pelvis 2019, 31(4):242–243.
2. Zimmerli W Trampuz A Ochsner PE Prosthetic-joint infections N Engl J Med 2004 351 16 1645 54 10.1056/NEJMra040181 15483283
Zimmerli W, Trampuz A, Ochsner PE. Prosthetic-joint infections. N Engl J Med. 2004;351(16):1645–54.15483283 10.1056/NEJMra040181
3. Huotari K Peltola M Jämsen E The incidence of late prosthetic joint infections: a registry-based study of 112,708 primary hip and knee replacements Acta Orthop 2015 86 3 321 5 10.3109/17453674.2015.1035173 25813645
Huotari K, Peltola M, Jämsen E. The incidence of late prosthetic joint infections: a registry-based study of 112,708 primary hip and knee replacements. Acta Orthop. 2015;86(3):321–5.25813645 10.3109/17453674.2015.1035173
4. Choi HJ Adiyani L Sung J Choi JY Kim HB Kim YK Kwak YG Yoo H Lee SO Han SH Five-year decreased incidence of surgical site infections following gastrectomy and prosthetic joint replacement surgery through active surveillance by the Korean nosocomial infection Surveillance System J Hosp Infect 2016 93 4 339 46 10.1016/j.jhin.2015.12.021 26944901
Choi HJ, Adiyani L, Sung J, Choi JY, Kim HB, Kim YK, Kwak YG, Yoo H, Lee SO, Han SH, et al. Five-year decreased incidence of surgical site infections following gastrectomy and prosthetic joint replacement surgery through active surveillance by the Korean nosocomial infection Surveillance System. J Hosp Infect. 2016;93(4):339–46.26944901 10.1016/j.jhin.2015.12.021
5. Parvizi J Pawasarat IM Azzam KA Joshi A Hansen EN Bozic KJ Periprosthetic joint infection: the economic impact of methicillin-resistant infections J Arthroplasty 2010 25 6 Suppl 103 7 10.1016/j.arth.2010.04.011 20570103
Parvizi J, Pawasarat IM, Azzam KA, Joshi A, Hansen EN, Bozic KJ. Periprosthetic joint infection: the economic impact of methicillin-resistant infections. J Arthroplasty. 2010;25(6 Suppl):103–7.20570103 10.1016/j.arth.2010.04.011
6. Parvizi J Tan TL Goswami K Higuera C Della Valle C Chen AF Shohat N The 2018 definition of Periprosthetic hip and knee infection: an evidence-based and validated Criteria J Arthroplasty 2018 33 5 1309 e13141302 10.1016/j.arth.2018.02.078 29551303
Parvizi J, Tan TL, Goswami K, Higuera C, Della Valle C, Chen AF, Shohat N. The 2018 definition of Periprosthetic hip and knee infection: an evidence-based and validated Criteria. J Arthroplasty. 2018;33(5):1309–e13141302.29551303 10.1016/j.arth.2018.02.078
7. Alamanda VK, Springer BD. The prevention of infection: 12 modifiable risk factors. Bone Joint J 2019, 101–b(1_Supple_A):3–9.
8. Avila A Acuña AJ Do MT Samuel LT Kamath AF Intra-articular injection receipt within 3 months prior to primary total knee arthroplasty is associated with increased periprosthetic joint infection risk Knee Surg Sports Traumatol Arthrosc 2022 30 12 4088 97 10.1007/s00167-022-06942-3 35325263
Avila A, Acuña AJ, Do MT, Samuel LT, Kamath AF. Intra-articular injection receipt within 3 months prior to primary total knee arthroplasty is associated with increased periprosthetic joint infection risk. Knee Surg Sports Traumatol Arthrosc. 2022;30(12):4088–97.35325263 10.1007/s00167-022-06942-3
9. Avila A Do MT Acuña AJ Samuel LT Kamath AF How do pre-operative intra-articular injections impact periprosthetic joint infection risk following primary total hip arthroplasty? A systematic review and meta-analysis Arch Orthop Trauma Surg 2023 143 3 1627 35 10.1007/s00402-022-04375-8 35150302
Avila A, Do MT, Acuña AJ, Samuel LT, Kamath AF. How do pre-operative intra-articular injections impact periprosthetic joint infection risk following primary total hip arthroplasty? A systematic review and meta-analysis. Arch Orthop Trauma Surg. 2023;143(3):1627–35.35150302 10.1007/s00402-022-04375-8
10. Wang Q Goswami K Shohat N Aalirezaie A Manrique J Parvizi J Longer Operative Time results in a higher rate of subsequent periprosthetic joint infection in patients undergoing primary joint arthroplasty J Arthroplasty 2019 34 5 947 53 10.1016/j.arth.2019.01.027 30765229
Wang Q, Goswami K, Shohat N, Aalirezaie A, Manrique J, Parvizi J. Longer Operative Time results in a higher rate of subsequent periprosthetic joint infection in patients undergoing primary joint arthroplasty. J Arthroplasty. 2019;34(5):947–53.30765229 10.1016/j.arth.2019.01.027
11. Tai DBG Patel R Abdel MP Berbari EF Tande AJ Microbiology of hip and knee periprosthetic joint infections: a database study Clin Microbiol Infect 2022 28 2 255 9 10.1016/j.cmi.2021.06.006 34129907
Tai DBG, Patel R, Abdel MP, Berbari EF, Tande AJ. Microbiology of hip and knee periprosthetic joint infections: a database study. Clin Microbiol Infect. 2022;28(2):255–9.34129907 10.1016/j.cmi.2021.06.006
12. Rochford ET Richards RG Moriarty TF Influence of material on the development of device-associated infections Clin Microbiol Infect 2012 18 12 1162 7 10.1111/j.1469-0691.2012.04002.x 22925523
Rochford ET, Richards RG, Moriarty TF. Influence of material on the development of device-associated infections. Clin Microbiol Infect. 2012;18(12):1162–7.22925523 10.1111/j.1469-0691.2012.04002.x
13. Harris LG Meredith DO Eschbach L Richards RG Staphylococcus aureus adhesion to standard micro-rough and electropolished implant materials J Mater Sci Mater Med 2007 18 6 1151 6 10.1007/s10856-007-0143-0 17268867
Harris LG, Meredith DO, Eschbach L, Richards RG. Staphylococcus aureus adhesion to standard micro-rough and electropolished implant materials. J Mater Sci Mater Med. 2007;18(6):1151–6.17268867 10.1007/s10856-007-0143-0
14. Grammatopoulos G, Bolduc ME, Atkins BL, Kendrick BJL, McLardy-Smith P, Murray DW, Gundle R, Taylor AH. Functional outcome of debridement, antibiotics and implant retention in periprosthetic joint infection involving the hip: a case-control study. Bone Joint J 2017, 99–b(5):614–622.
15. Bedair HS Katakam A Bedeir YH Yeroushalmi D Schwarzkopf R A decision analysis of treatment strategies for acute periprosthetic joint infection: early irrigation and debridement versus delayed treatment based on organism J Orthop 2020 22 246 50 10.1016/j.jor.2020.04.003 32425426
Bedair HS, Katakam A, Bedeir YH, Yeroushalmi D, Schwarzkopf R. A decision analysis of treatment strategies for acute periprosthetic joint infection: early irrigation and debridement versus delayed treatment based on organism. J Orthop. 2020;22:246–50.32425426 10.1016/j.jor.2020.04.003
16. Cooper HJ. CJ Della Valle 2013 The two-stage standard in revision total hip replacement. Bone Joint J 95-b 11 Suppl A 84–7.
17. Sporer SM Spacer Design options and consideration for Periprosthetic Joint infection J Arthroplasty 2020 35 3s S31 4 10.1016/j.arth.2019.11.007 32046828
Sporer SM. Spacer Design options and consideration for Periprosthetic Joint infection. J Arthroplasty. 2020;35(3s):S31–4.32046828 10.1016/j.arth.2019.11.007
18. Citak M Argenson JN Masri B Kendoff D Springer B Alt V Baldini A Cui Q Deirmengian GK del Sel H Spacers J Orthop Res 2014 32 Suppl 1 S120 129 24464885
Citak M, Argenson JN, Masri B, Kendoff D, Springer B, Alt V, Baldini A, Cui Q, Deirmengian GK, del Sel H, et al. Spacers. J Orthop Res. 2014;32(Suppl 1):S120–129.24464885
19. Tan TL, Goswami K, Kheir MM, Xu C, Wang Q, Parvizi J. Surgical Treatment of Chronic Periprosthetic Joint Infection: Fate of Spacer Exchanges. J Arthroplasty 2019, 34(9):2085–2090.e2081.
20. Burnett RS Kelly MA Hanssen AD Barrack RL Technique and timing of two-stage exchange for infection in TKA Clin Orthop Relat Res 2007 464 164 78 10.1097/BLO.0b013e318157eb1e 17975376
Burnett RS, Kelly MA, Hanssen AD, Barrack RL. Technique and timing of two-stage exchange for infection in TKA. Clin Orthop Relat Res. 2007;464:164–78.17975376 10.1097/BLO.0b013e318157eb1e
21. Winkler T Stuhlert MGW Lieb E Müller M von Roth P Preininger B Trampuz A Perka CF Outcome of short versus long interval in two-stage exchange for periprosthetic joint infection: a prospective cohort study Arch Orthop Trauma Surg 2019 139 3 295 303 10.1007/s00402-018-3052-4 30443674
Winkler T, Stuhlert MGW, Lieb E, Müller M, von Roth P, Preininger B, Trampuz A, Perka CF. Outcome of short versus long interval in two-stage exchange for periprosthetic joint infection: a prospective cohort study. Arch Orthop Trauma Surg. 2019;139(3):295–303.30443674 10.1007/s00402-018-3052-4
22. Kunutsor SK Whitehouse MR Blom AW Beswick AD Re-infection outcomes following one- and two-stage Surgical revision of infected hip prosthesis: a systematic review and Meta-analysis PLoS ONE 2015 10 9 e0139166 10.1371/journal.pone.0139166 26407003
Kunutsor SK, Whitehouse MR, Blom AW, Beswick AD. Re-infection outcomes following one- and two-stage Surgical revision of infected hip prosthesis: a systematic review and Meta-analysis. PLoS ONE. 2015;10(9):e0139166.26407003 10.1371/journal.pone.0139166
23. Kunutsor SK Whitehouse MR Blom AW Board T Kay P Wroblewski BM Zeller V Chen SY Hsieh PH Masri BA One- and two-stage surgical revision of peri-prosthetic joint infection of the hip: a pooled individual participant data analysis of 44 cohort studies Eur J Epidemiol 2018 33 10 933 46 10.1007/s10654-018-0377-9 29623671
Kunutsor SK, Whitehouse MR, Blom AW, Board T, Kay P, Wroblewski BM, Zeller V, Chen SY, Hsieh PH, Masri BA, et al. One- and two-stage surgical revision of peri-prosthetic joint infection of the hip: a pooled individual participant data analysis of 44 cohort studies. Eur J Epidemiol. 2018;33(10):933–46.29623671 10.1007/s10654-018-0377-9
24. Kildow BJ, Springer BD, Brown TS, Lyden E, Fehring TK, Garvin KL. Long Term results of two-stage revision for chronic periprosthetic hip infection: a Multicenter Study. J Clin Med 2022, 11(6).
25. Puetzler J Schulze M Gosheger G Schwarze J Moellenbeck B Theil C Is long time to reimplantation a risk factor for reinfection in two-stage revision for periprosthetic infection? A systematic review of the literature Front Surg 2023 10 1113006 10.3389/fsurg.2023.1113006 36874470
Puetzler J, Schulze M, Gosheger G, Schwarze J, Moellenbeck B, Theil C. Is long time to reimplantation a risk factor for reinfection in two-stage revision for periprosthetic infection? A systematic review of the literature. Front Surg. 2023;10:1113006.36874470 10.3389/fsurg.2023.1113006
26. Shi T Chen Z Hu D Wu D Wang Z Liu W Concomitant malnutrition and frailty are significant risk factors for poor outcome following two-stage revision for chronic periprosthetic joint infection J Orthop Surg Res 2023 18 1 804 10.1186/s13018-023-04293-4 37891602
Shi T, Chen Z, Hu D, Wu D, Wang Z, Liu W. Concomitant malnutrition and frailty are significant risk factors for poor outcome following two-stage revision for chronic periprosthetic joint infection. J Orthop Surg Res. 2023;18(1):804.37891602 10.1186/s13018-023-04293-4
27. Stambough JB Curtin BM Odum SM Cross MB Martin JR Fehring TK Does change in ESR and CRP guide the timing of two-stage Arthroplasty Reimplantation? Clin Orthop Relat Res 2019 477 2 364 71 10.1097/01.blo.0000533618.31937.45 30566107
Stambough JB, Curtin BM, Odum SM, Cross MB, Martin JR, Fehring TK. Does change in ESR and CRP guide the timing of two-stage Arthroplasty Reimplantation? Clin Orthop Relat Res. 2019;477(2):364–71.30566107 10.1097/01.blo.0000533618.31937.45
28. Houdek MT Wagner ER Watts CD Osmon DR Hanssen AD Lewallen DG Mabry TM Morbid obesity: a significant risk factor for failure of two-stage revision total hip arthroplasty for infection J Bone Joint Surg Am 2015 97 4 326 32 10.2106/JBJS.N.00515 25695985
Houdek MT, Wagner ER, Watts CD, Osmon DR, Hanssen AD, Lewallen DG, Mabry TM. Morbid obesity: a significant risk factor for failure of two-stage revision total hip arthroplasty for infection. J Bone Joint Surg Am. 2015;97(4):326–32.25695985 10.2106/JBJS.N.00515
29. Khury F, Oltmanns M, Fuchs M, Leiprecht J, Reichel H, Faschingbauer M. Against the Norm: Do Not Rely on Serum C-Reactive Protein and White Blood Cell Count Only When Assessing Eradication of Periprosthetic Joint Infection. Antibiotics (Basel) 2022, 11(9).
30. Mederake M, Hofmann UK, Benda S, Schuster P, Fink B. Diagnostic value of CRP and serum WBC Count during Septic two-stage revision of total hip arthroplasties. Antibiot (Basel) 2022, 11(8).
31. Matar HE, Bloch BV, Snape SE, James PJ. Outcomes of single- and two-stage revision total knee arthroplasty for chronic periprosthetic joint infection: long-term outcomes of changing clinical practice in a specialist centre. Bone Joint J 2021, 103–b(8):1373–1379.
32. Wang Q Huang J Chen X Jin Y Risk factors of reinfection after prosthesis removal and antibiotic bone cement spacer implantation for the treatment of periprosthetic joint infection BMC Infect Dis 2022 22 1 905 10.1186/s12879-022-07908-z 36471324
Wang Q, Huang J, Chen X, Jin Y. Risk factors of reinfection after prosthesis removal and antibiotic bone cement spacer implantation for the treatment of periprosthetic joint infection. BMC Infect Dis. 2022;22(1):905.36471324 10.1186/s12879-022-07908-z
33. 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 36 10.1111/iwj.12640 27397553
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):529–36.27397553 10.1111/iwj.12640
34. Lin YC Lin YH Chou JH Lo YT Chang CH Lee SH Lin SH Higher reinfection rate after two-stage revision arthroplasty in patients with refractory diabetes mellitus: a retrospective analysis with a minimum ten-year follow up BMC Musculoskelet Disord 2022 23 1 990 10.1186/s12891-022-05964-9 36397029
Lin YC, Lin YH, Chou JH, Lo YT, Chang CH, Lee SH, Lin SH. Higher reinfection rate after two-stage revision arthroplasty in patients with refractory diabetes mellitus: a retrospective analysis with a minimum ten-year follow up. BMC Musculoskelet Disord. 2022;23(1):990.36397029 10.1186/s12891-022-05964-9
35. Berthold E Geborek P Gülfe A Continuation of TNF blockade in patients with inflammatory rheumatic disease. An observational study on surgical site infections in 1,596 elective orthopedic and hand surgery procedures Acta Orthop 2013 84 5 495 501 10.3109/17453674.2013.842431 24032521
Berthold E, Geborek P, Gülfe A. Continuation of TNF blockade in patients with inflammatory rheumatic disease. An observational study on surgical site infections in 1,596 elective orthopedic and hand surgery procedures. Acta Orthop. 2013;84(5):495–501.24032521 10.3109/17453674.2013.842431
36. Grennan DM Gray J Loudon J Fear S Methotrexate and early postoperative complications in patients with rheumatoid arthritis undergoing elective orthopaedic surgery Ann Rheum Dis 2001 60 3 214 7 10.1136/ard.60.3.214 11171680
Grennan DM, Gray J, Loudon J, Fear S. Methotrexate and early postoperative complications in patients with rheumatoid arthritis undergoing elective orthopaedic surgery. Ann Rheum Dis. 2001;60(3):214–7.11171680 10.1136/ard.60.3.214
37. Yurube T Takahi K Owaki H Fuji T Kurosaka M Doita M Late infection of total knee arthroplasty inflamed by anti-TNFalpha, infliximab therapy in rheumatoid arthritis Rheumatol Int 2010 30 3 405 8 10.1007/s00296-009-0948-x 19449010
Yurube T, Takahi K, Owaki H, Fuji T, Kurosaka M, Doita M. Late infection of total knee arthroplasty inflamed by anti-TNFalpha, infliximab therapy in rheumatoid arthritis. Rheumatol Int. 2010;30(3):405–8.19449010 10.1007/s00296-009-0948-x
38. Gabrielli AS Wilson AE Wawrose RA Dombrowski M O’Malley MJ Klatt BA The presence of a draining sinus is associated with failure of re-implantation during two-stage exchange arthroplasty J Bone Jt Infect 2022 7 2 55 60 10.5194/jbji-7-55-2022 35402147
Gabrielli AS, Wilson AE, Wawrose RA, Dombrowski M, O’Malley MJ, Klatt BA. The presence of a draining sinus is associated with failure of re-implantation during two-stage exchange arthroplasty. J Bone Jt Infect. 2022;7(2):55–60.35402147 10.5194/jbji-7-55-2022
39. Hartzler MA, Li K, Geary MB, Odum SM, Springer BD. Complications in the treatment of prosthetic joint infection. Bone Joint J 2020, 102–b(6_Supple_A):145–150.
40. Berend KR Lombardi AV Jr Morris MJ Bergeson AG Adams JB Sneller MA Two-stage treatment of hip periprosthetic joint infection is associated with a high rate of infection control but high mortality Clin Orthop Relat Res 2013 471 2 510 8 10.1007/s11999-012-2595-x 22983683
Berend KR, Lombardi AV Jr., Morris MJ, Bergeson AG, Adams JB, Sneller MA. Two-stage treatment of hip periprosthetic joint infection is associated with a high rate of infection control but high mortality. Clin Orthop Relat Res. 2013;471(2):510–8.22983683 10.1007/s11999-012-2595-x
41. Klemt C Padmanabha A Esposito JG Laurencin S Smith EJ Kwon YM Elevated ESR and CRP prior to second-stage reimplantation knee revision surgery for Periprosthetic Joint Infection Are Associated with increased reinfection rates J Knee Surg 2023 36 4 354 61 10.1055/s-0041-1733902 34375998
Klemt C, Padmanabha A, Esposito JG, Laurencin S, Smith EJ, Kwon YM. Elevated ESR and CRP prior to second-stage reimplantation knee revision surgery for Periprosthetic Joint Infection Are Associated with increased reinfection rates. J Knee Surg. 2023;36(4):354–61.34375998 10.1055/s-0041-1733902
42. Paz Z Zhu C Lieber SB Fowler ML Shmerling RH Presentation and outcomes of Peri-prosthetic Joint infection: a comparison of culture-positive and culture-negative disease Surg Infect (Larchmt) 2021 22 8 828 35 10.1089/sur.2020.302 33689447
Paz Z, Zhu C, Lieber SB, Fowler ML, Shmerling RH. Presentation and outcomes of Peri-prosthetic Joint infection: a comparison of culture-positive and culture-negative disease. Surg Infect (Larchmt). 2021;22(8):828–35.33689447 10.1089/sur.2020.302
43. Wang J Wang Q Shen H Zhang X Comparable outcome of culture-negative and culture-positive periprosthetic hip joint infection for patients undergoing two-stage revision Int Orthop 2018 42 3 469 77 10.1007/s00264-018-3783-4 29397413
Wang J, Wang Q, Shen H, Zhang X. Comparable outcome of culture-negative and culture-positive periprosthetic hip joint infection for patients undergoing two-stage revision. Int Orthop. 2018;42(3):469–77.29397413 10.1007/s00264-018-3783-4
44. Kim CW Lee CR Park DH Kim DY Kim JW Clinical outcomes of two-stage revision for chronic periprosthetic joint infection of the knee: culture-negative versus culture-positive Knee Surg Relat Res 2021 33 1 28 10.1186/s43019-021-00112-4 34479655
Kim CW, Lee CR, Park DH, Kim DY, Kim JW. Clinical outcomes of two-stage revision for chronic periprosthetic joint infection of the knee: culture-negative versus culture-positive. Knee Surg Relat Res. 2021;33(1):28.34479655 10.1186/s43019-021-00112-4
45. Wimmer MD Friedrich MJ Randau TM Ploeger MM Schmolders J Strauss AA Hischebeth GT Pennekamp PH Vavken P Gravius S Polymicrobial infections reduce the cure rate in prosthetic joint infections: outcome analysis with two-stage exchange and follow-up ≥ two years Int Orthop 2016 40 7 1367 73 10.1007/s00264-015-2871-y 26183140
Wimmer MD, Friedrich MJ, Randau TM, Ploeger MM, Schmolders J, Strauss AA, Hischebeth GT, Pennekamp PH, Vavken P, Gravius S. Polymicrobial infections reduce the cure rate in prosthetic joint infections: outcome analysis with two-stage exchange and follow-up ≥ two years. Int Orthop. 2016;40(7):1367–73.26183140 10.1007/s00264-015-2871-y
46. Bozhkova S Tikhilov R Labutin D Denisov A Shubnyakov I Razorenov V Artyukh V Rukina A Failure of the first step of two-stage revision due to polymicrobial prosthetic joint infection of the hip J Orthop Traumatol 2016 17 4 369 76 10.1007/s10195-016-0417-8 27387172
Bozhkova S, Tikhilov R, Labutin D, Denisov A, Shubnyakov I, Razorenov V, Artyukh V, Rukina A. Failure of the first step of two-stage revision due to polymicrobial prosthetic joint infection of the hip. J Orthop Traumatol. 2016;17(4):369–76.27387172 10.1007/s10195-016-0417-8
47. Hartman CW Daubach EC Richard BT Lyden ER Haider H Kildow BJ Konigsberg BS Garvin KL Predictors of Reinfection in Prosthetic Joint infections following two-stage Reimplantation J Arthroplasty 2022 37 7s S674 7 10.1016/j.arth.2022.03.017 35283230
Hartman CW, Daubach EC, Richard BT, Lyden ER, Haider H, Kildow BJ, Konigsberg BS, Garvin KL. Predictors of Reinfection in Prosthetic Joint infections following two-stage Reimplantation. J Arthroplasty. 2022;37(7s):S674–7.35283230 10.1016/j.arth.2022.03.017
