The Journal of Arthroplasty 35 (2020) S9eS13

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The Journal of Arthroplasty

journal homepage: www.arthroplastyjournal.org

Evolution of Diagnostic Definitions for Periprosthetic Joint

Infection in Total Hip and Knee Arthroplasty
Jesus M. Villa, MD a, Tejbir S. Pannu, MD, MS a, Nicolas Piuzzi, MD b,
Aldo M. Riesgo, MD a, Carlos A. Higuera, MD a, *
a
Levitetz Department of Orthopaedic Surgery, Cleveland Clinic Florida, Weston, FL
b
Department of Orthopaedic Surgery, Cleveland Clinic, Cleveland, OH

a r t i c l e i n f o a b s t r a c t

Article history: Various definitions and biomarkers have been developed in an unsuccessful attempt to obtain a “gold
Received 7 October 2019 standard” for periprosthetic joint infection (PJI) diagnosis. The development of the 2011 Musculoskeletal
Received in revised form Infection Society criteria facilitated further research and advances by allowing the use of a consistent PJI
17 October 2019
definition across studies. The newly proposed 2018 criteria do not rely at all on expert opinions/
Accepted 19 October 2019
consensus. In this review, we describe the most relevant definitions developed throughout recent time,
their rationale, characteristics, and supportive evidence for their clinical implementation. In the opinion
of the authors, the orthopedic community should consider a probability and likelihood paradigm to
Keywords:
periprosthetic joint infection
create a PJI diagnostic definition. Probably not a single definition might be suited for all situations; the
PJI inclusion of serological findings could be the next step moving forward.
definition of PJI © 2019 Published by Elsevier Inc.
total hip arthroplasty
total knee arthroplasty

Periprosthetic joint infection (PJI) is one of the most catastrophic
complications in total hip and knee arthroplasty. The healthcare
costs of PJI management have been valued at more than $566
million, and it is projected to exceed $1.62 billion by the year 2020
[1]. Thus, an accurate and timely diagnosis of PJI is imperative for
surgical planning and satisfactory clinical results. In 2011, the
Musculoskeletal Infection Society (MSIS) developed the first stan-
dardized definition of PJI which paved the way for further in-
vestigations and developments by making comparisons between
different studies possible, thanks to the use of a consistent defini-
tion of PJI [2]. This definition was later endorsed and slightly
modified by the International Consensus Meeting (ICM) in 2013 [3].
Both criteria comprised clinical examination findings, preoperative
serum and synovial tests, and intraoperative results. But about the
same time, in 2012, the Infection Disease Society of America (IDSA)
This article is published as part of a supplement supported by an educational grant
from OsteoRemedies, LLC.
proposed a set of clinical practice guidelines for the diagnosis of PJI
[4]. Recently, in 2018, a new definition based on a weighted-scoring
system was developed using the MSIS criteria as a reference. This
new definition was not based on expert opinions or consensus, and
it was validated in a series of patients [5]. In the last decade, a
number of biomarkers for the diagnosis of infection have also been
tested out of which alpha-defensin seems to be the one with the
best diagnostic performance [6]. Widespread acceptance of other
biomarkers for PJI diagnosis has been limited by costs and insuffi-
cient reproducibility.
Regrettably, there is sometimes confusion among adult recon-
structive orthopedic surgeons because of the diverse milieu of PJI
definitions. Up to this date, there is no single definition universally
accepted. As a result, the purpose of the current review is to
describe the most relevant definitions of PJI developed throughout
recent time, the rationale behind their creation, their characteris-
tics, and the supportive evidence for their implementation in the
clinical practice.

One or more of the authors of this paper have disclosed potential or pertinent
conflicts of interest, which may include receipt of payment, either direct or indirect, Materials and Methods
institutional support, or association with an entity in the biomedical field which
may be perceived to have potential conflict of interest with this work. For full
disclosure statements refer to https://doi.org/10.1016/j.arth.2019.10.032.
To ascertain the most important definitions and biomarkers for
* Reprint requests: Carlos A. Higuera, MD, Cleveland Clinic Florida, 2950 Cleve- the diagnosis of PJI, a literature search of all relevant papers pub-
land Clinic Blvd., Weston, FL, 33331. lished and listed in the PUBMED database between January 1, 2009

https://doi.org/10.1016/j.arth.2019.10.032
0883-5403/© 2019 Published by Elsevier Inc.
S10 J.M. Villa et al. / The Journal of Arthroplasty 35 (2020) S9eS13
and September 24, 2019 was performed using the following key-
words: “Diagnosis of Periprosthetic Joint Infection” (n ¼ 1375),
“Diagnosis and Periprosthetic and Joint and Infection” (n ¼ 1375),
“Diagnosis of PJI in Hip and Knee Joints” (n ¼ 292), “Diagnostic
Criteria for Periprosthetic Joint Infection” (n ¼ 296), and “Definition
of Periprosthetic Joint Infection” (n ¼ 86). The title and abstract of
the publications that seemed pertinent to the subject were
reviewed. Only English language articles that reported infection as
a topic of focus, purpose of investigation, and/or critical finding
were included. Articles that addressed PJI as an incidental finding or
were solely based on expert opinion were excluded.
Each definition of infection was reviewed in detail and pre-
sented to the reader in this review in line with the original publi-
cation. Furthermore, the most prominent serum and synovial
biomarkers used for the diagnosis of PJI, and the scientific evidence
behind them, are also presented. Finally, we give our opinion
regarding the different PJI definitions and the utility of the different
biomarkers used to diagnose infection and provide further rec-
ommendations for future investigations.
Results
Musculoskeletal Infection Society 2011
The MSIS convened at its 21st Annual Meeting (August 4, 2011) a
workshop to create a single standard definition of PJI based on the
evidence available at that time. The proposed criteria were the initial
standardization against which new tests to diagnose PJI could be
measured. According to it, a definitive PJI diagnosis exists when
there is a sinus tract communicating with the joint or when a single
organism is isolated by culture from 2 or more separate tissue or
fluid samples or when 4 out of 6 minor criteria are present, as shown
in Table 1. Of note, the workgroup emphasized that PJI may still be
present even if fewer than 4 of these criteria are met [2].
There are important considerations in regard to the 2011 MSIS
criteria. Each of the 3 to 5 samples for cultures (from representative
periprosthetic tissue/fluid) should be taken with separate sterile
instruments, and fungal/mycobacterial cultures should be done
routinely only in higher-risk scenarios. In the absence of other
criteria, isolation of a single low virulence organism such as Cor-
ynebacteria, Cutibacterium acnes, or coagulase-negative Staphylo-
coccus does not necessarily represent PJI. On the other hand,
isolation of a single virulent organism such as Staphylococcus aureus
may represent infection. In this definition, there were no concrete
and definitive proposed thresholds of the serum and synovial tests.
The workgroup acknowledged that histologic examination of per-
iprosthetic tissues may be operator-dependent and that the
Table 1
2011 Musculoskeletal Infection Society (MSIS) PJI Criteria.
Periprosthetic Joint Infection Exists When:
1. There is a sinus tract communicating with the prosthesis; OR
2. A pathogen is isolated by culture from at least 2 separate tissue or
fluid samples obtained from the affected prosthetic joint; OR
3. When 4 of the following 6 criteria exist:
a) Elevated serum erythrocyte sedimentation rate (ESR) and serum
C-reactive protein (CRP) concentration,
b) Elevated synovial leukocyte count,
c) Elevated synovial neutrophil percentage (PMN%),
d) Presence of purulence in the affected joint,
e) Isolation of a microorganism in one culture of periprosthetic tissue
or fluid, or
f) Greater than 5 neutrophils per high-power field in five high-power
fields observed from histologic analysis of periprosthetic tissue
at 400 magnification.
Note: Periprosthetic joint infection may still be present if less than 4 criteria are met.
proposed criteria might require modification as new tests and
techniques become validated and widely available [2].
Infectious Diseases Society of America 2012
In 2012, the IDSA proposed evidence-based and opinion-based
clinical practice guidelines for the diagnosis of PJI [4]. The panel
weighted the quality of the evidence and the grade of recommen-
dation. According to these guidelines, PJI was definitively present
when in presence of a sinus tract communicating with the pros-
thesis or purulence without any other known etiology. Two or more
preoperative aspiration/intraoperative cultures of the same or-
ganism (based on genus and species identification or common
antibiogram) were also considered definitive evidence of infection.
The growth of a single virulent organism (ie, S aureus) may repre-
sent PJI. Acute inflammation as observed on histopathologic ex-
amination of periprosthetic tissue was highly suggestive of
infection. The panel recognized that infection was still possible
even if these criteria were not met [4].
International Consensus Meeting 2013 (Modified MSIS)
In August 2013, a consensus group made up of 400 experts from
52 countries met in Philadelphia, Pennsylvania, as part of an ICM on
PJI. The consensus group adopted the proposed 2011 MSIS criteria
and slightly modified it. The leukocyte esterase test was added as
one of the minor criterion while purulence was removed. Most
importantly, the workgroup determined the thresholds for the
minor diagnostic criteria based on the acuity of infection (less or
more than 90 days from the index surgery) and stated that there
was no difference in this regard between total knee and hip
arthroplasties (Table 2) [3].
In the last decade, various biomarkers for the diagnosis of PJI
have been investigated. Saleh et al performed a systematic review
and meta-analysis of all synovial fluid markers used for the diag-
nosis of infection [6]. Among these, alpha-defensin had the best
diagnostic performance. The odds of a positive alpha-defensin
result among infected patients was found to be 748.3 times
higher than the odds of the same result among patients without
infection. However, this result was not found to be a statistically
significant difference when compared with the ones of the other
biomarkers because of overlapping 95% confidence intervals.
Table 2
2013 International Consensus Meeting (ICM) PJI Criteria.
Periprosthetic Joint Infection Exists when 1 of the Major Criteria or 3 out of the 5
Minor Criteria Exist
Major criteria
- There is a sinus tract communicating with the joint; OR
- Two positive periprosthetic cultures with phenotypically
identical organisms; OR
Minor criteria
1. Elevated serum ESR (no threshold for acute PJI and 30 mm/h for chronic
PJI) and CRP (100 mg/L for acute PJI and 10 mg/L for chronic PJI),
2. Elevated synovial fluid WBC count (10,000 cells/mL for acute PJI and 3000
for chronic PJI) OR þ or þþ change on leukocyte esterase test strip
(for both, acute and chronic PJI),
3. Elevated synovial fluid PMN% (90% for acute PJI and 80% for chronic PJI),
4. Positive histologic analysis of periprosthetic tissue (>5 neutrophils per
high-power field in 5 high-power fields (400) for both, acute and
chronic PJI),
5. A single positive culture.
Notes
-Periprosthetic joint infection may still be present without meeting these
criteria, particularly in the case of less virulent organisms such as
Cutibacterium acnes.
- Acute PJI (<90 d) and chronic PJI (>90 d).
 J.M. Villa et al. / The Journal of Arthroplasty 35 (2020) S9eS13 S11

Table 3 results in cases with metal-on-metal implants [8e10]. The original

2018 International Consensus Meeting (ICM) PJI Criteria. MSIS criteria was slightly modified by the ICM on PJI in 2013, and
Major Criteria among other changes, it included the addition of specific thresholds
1. Two positive cultures of the same organism; OR Decision
for the different tests (for both, acute and chronic infections) that
2. Sinus tract with evidence of communication PJI make part of it [2,3]. Currently, the 2013 ICM definition is the most
to the joint or visualization of the joint prosthesis; OR commonly used for clinical and research purposes. Notwith-
Minor criteria standing, this modified MSIS definition has also proven unsuc-
cessful for the diagnosis of infection in certain situations. George
A. Preoperative diagnosis Score Decision
et al investigated the diagnostic accuracy of the 2013 ICM definition
Serum 6 : PJI in predicting failure of reimplantation (second stage) at a minimum
1. [ CRP (>1 mg/dL) OR D-Dimer (>860 ng/mL) 2 2-5: Possibly PJIa
2. [ ESR (>30 mm/h) 1 0-1: No PJI
follow-up of 1 year. The study included 79 patients (38 knees and
Synovial 41 hips) with diagnosis of PJI according to these criteria [11]. The
1. [ Synovial WBC count (>3000 cells/mL) 3 endpoint was success which was defined as controlled infection
or LE (þþ) (healed wound with no fistula/drainage/pain), no revision surgery,
2. Positive alpha-defensin (signal-to-cut-off 3
and no mortality associated with PJI. The 2013 ICM definition
ratio >1)
3. [ Synovial PMN% (>80%) 2 demonstrated high specificity (96%) but very low sensitivity (26%)
4. [ Synovial CRP (>6.9 mg/L) 1 at reimplantation [11]. Similarly, Frangiamore et al tested the per-
B. Intraoperative diagnosisa
formance of the 2013 ICM criteria (modified MSIS) in confirming
the resolution of infection before reimplantation in 31 patients
1. Preoperative score - 6: PJI
undergoing 2-stage exchange arthroplasty [12]. The “Delphi”
2. Positive histology 3 4-5: Inconclusive PJI
3. Positive purulence 3 3: No PJI consensus-based criteria were used to define success of reimplan-
4. Single positive culture 2 tation at a minimum follow-up of 1 year [13]. There were 4 reim-
C-reactive protein (CRP); Erythrocyte sedimentation rate (ESR); Positive (þ); [:
plantation patients who failed treatment, and in all of them, the
Increase; Polymorphonuclear neutrophils (PMN). 2013 ICM definition was unable to identify a single case of infection
a
For those patients with inconclusive minor criteria, operative criteria may be (sensitivity ¼ 0). However, the specificity was 89% [12]. Kheir et al
included for refuting or confirming PJI diagnosis. also showed that the use of the ICM definition provided a low
sensitivity (25%) when treatment failure was defined according to
the Delphi criteria [14]. Thus, the 2013 ICM definition (modified
International Consensus Meeting 2018
MSIS criteria) has been shown to have a limited value in screening
for infection resolution before reimplantation. Similarly, there are
The previous definitions of PJI, though based on the evidence
no specific biomarkers that are good predictors of failures after
available at that time, were also based on expert opinions and/or
reimplantation [15]. Nevertheless, it is important to note that not
consensus. The “gold standard” definition remained elusive, and
all failures could have been attributed to the original infection that
with the advent of new diagnostic tests, an updated weight-
was supposedly missed; they could have been new infections
adjusted scoring system to define PJI for hips and knees was
identified during the follow-up. This is a limitation in the meth-
warranted. This circumstance prompted the development of
odology of all these studies, that if addressed (maybe with geno-
evidence-based criteria. Using the MSIS criteria as a reference, a
typic identification of the infectious organisms), more definitive
multiinstitutional study was performed at 3 academic institutions
conclusions could be drawn.
in patients undergoing hip and knee revision arthroplasty. This
The IDSA also published a set of clinical practice guidelines to
definition was validated in 200 aseptic patients and a cohort of 222
establish the diagnosis of PJI [4]. Even though this definition has
patients with PJI who subsequently failed because of reinfection [5].
been cited a number of times in the literature, to the best of our
Relative weight for each biomarker was generated making use of a
knowledge, no study has evaluated its clinical efficacy when it
stepwise approach using random forest analysis and multivariate
comes to detect infection or predict the success of revision
regression. Preoperative and intraoperative criteria were defined
including reimplantation.
(Table 3). In these newly proposed criteria, 2 positive cultures of the
It is also imperative to bring attention to particular tests that
same organism or a sinus tract communicating with the joint or the
make part of previous or current definitions used for the diagnosis
visualization of the prosthesis is definitive evidence of infection in a
of PJI. Frozen section is one of the oldest tests utilized to establish
similar manner to prior proposed criteria (major criteria).
the diagnosis of infection and it is a minor criterion under the 2011
Regarding preoperative and intraoperative minor criteria, a scoring
MSIS and 2013 ICM definitions. A meta-analysis of 26 studies (3269
system is used to define infection. A total score 6 defined infec-
patients) investigated the importance of intraoperative frozen
tion; a score between 2 and 5 is considered inconclusive and re-
section histopathology in the diagnosis of infection. When using
quires the inclusion of intraoperative criteria to confirm or refute
the 2011 MSIS criteria threshold (greater than 5 PMNs per high-
PJI diagnosis. A score of 0 or 1 does not define infection (Table 3).
power field), frozen section had 52.6 times higher odds of a posi-
This definition was presented during the second ICM where it
tive result in PJI cases than in aseptic cases [16]. Recently, Kwiecien
reached a “weak consensus,” only 68% [7]. This definition has not
et al showed that intraoperative frozen section histology has high
been endorsed by the MSIS.
specificity (98.8%) and moderate sensitivity (73.7%) compared with
the MSIS criteria [17]. Frozen sections seem to perform better as a
Discussion rule-in test than as a rule-out test. Their main limitation is that they
are operator-dependent.
Currently, there is no “gold standard” definition for the diag- Because none of the definitions (including the 2013 ICM criteria)
nosis of PJI. The development of the MSIS criteria in 2011 facilitated have shown good sensitivity to rule out infection, many biomarkers
further research by allowing the use of a consistent definition of have been investigated in an attempt to fill that void. A recent
infection across the studies. It was an important milestone; un- meta-analysis reviewed the utility of synovial biomarkers in the
fortunately, this “gold standard” was far from perfect. In clinical diagnosis of PJI. Alpha-defensin, C-reactive protein (CRP), leukocyte
practice, the original MSIS definition produced false-positive esterase, interleukin (IL)-6, IL-1b, and IL-17 showed high odds
S12 J.M. Villa et al. / The Journal of Arthroplasty 35 (2020) S9eS13
ratios for the diagnosis of infection. However, alpha-defensin
demonstrated the best diagnostic performance with 748.3 times
higher odds of a positive result in patients with PJI than in those
without infection [6]. Gehrke et al prospectively evaluated in 223
consecutive patients with painful THA or TKA a new rapid lateral
flow version of the alpha-defensin tests that allows in minutes to
detect high levels in synovial fluid [18]. The alpha-defensin results
from the aspirates were compared with MSIS criteria which were
considered the “gold standard” to diagnose PJI in that investigation.
The overall sensitivity of alpha-defensin was 92.1%, the specificity
and positive predictive value were 100%, whereas the negative
predictive value was 95.2% with an overall accuracy of 96.9%. These
findings allowed the authors to conclude that this new version of
alpha-defensin has a high accuracy for the diagnosis of infection. In
another recent publication, the performance of alpha-defensin was
compared with the MSIS, IDSA, and the proposed European Bone
and Joint Infection Society (EBJIS) definitions of PJI. Alpha-defensin
showed high specificity (>95%) but limited sensitivity (84% when
compared with MSIS, 67% with IDSA, and 54% with EBJIS). The
authors recommended the use of alpha-defensin as a confirmatory
test rather than as a screening test for the diagnosis of infection
[19]. Another biomarker that has gained attention in the orthopedic
community for PJI diagnosis is serum D-dimer. With the optimal
threshold of 850 ng/mL, serum D-dimer outperformed ESR and CRP
with a sensitivity of 89% and a specificity of 93% (ESR, 73% and 79%
and CRP 78% and 80%, respectively) [20]. However, these results
have not been reproduced, and 2 additional studies found that
plasma D-dimer may have a very poor diagnostic utility for PJI
whereas plasma fibrinogen seems to show better performance
[21,22].
Despite all previous efforts concerning the different definitions
of PJI and the development and testing of new biomarkers, there
are still no definitive criteria or test that fulfills the whole definition
of a “gold standard” for the diagnosis of PJI. As a result of this, a new
attempt was made in 2018 with the development of a new set of
criteria that, contrary to the previous definitions, did not rely on
consensus or expert opinions but actually on the findings obtained
through internal and external validation in a series of patients. The
main objective was to improve sensitivity without compromising
specificity. The 2018 PJI definition was developed and validated in a
cohort of patients through a multicenter collaboration [5]. This new
definition demonstrated an overall sensitivity and specificity of
97.7% (95% CI 94.7%-99.3%) and 99.5% (95% CI 97.3%-99.9%),
respectively. When comparing the new criteria with the 2011 MSIS
and 2013 ICM definitions considered as the “gold standard,” it
revealed similar specificity but higher sensitivity [2018 Definition
vs ICM (97.7% vs 86.9%); 2018 Definition vs MSIS (99.5% vs 79.3%)].
The new proposed definition was externally validated in a series of
222 PJI revisions and 200 aseptic cases. In total, 95.5% of infected
revisions were correctly diagnosed (true positives) while false and
inconclusive diagnoses were low (2.3%, each). In aseptic revisions,
97.5% of them were correctly identified (true negatives) with only 1
out of the 200 aseptic revisions being wrongly diagnosed (false
positive). In just 2% of the cases, a definitive diagnosis could not be
made [5]. However, given the lack of availability and significant
financial expenses associated with some biomarkers used for this
particular definition, its universal adoption seems difficult. Not to
mention the lack of reproducible data supporting the use of D-
Dimer [21,22].
In conclusion, the “gold standard” definition for the diagnosis of
PJI remains elusive. Most definitions developed up to date have
made use of a dichotomous paradigm (infected or not infected). It is
the opinion of the authors that the orthopedic community should
consider a probability and likelihood paradigm to create a defini-
tion for the diagnosis of infection. It is always crucial for surgeons to
have an in-depth understanding of the different definitions, their
applicability, and their limitations. Evidence-based biomarkers play
a fundamental role in the diagnosis of PJI; however, we cannot rely
exclusively upon them for the diagnosis of infection. There is hope
that new molecular technologies such as next-generation
sequencing (microbial DNA in a sample) could truly revolutionize
pathogen identification. Future research should also consider the
possibility of the development of a different PJI definition for spe-
cific situations. For example, a definition might be very valuable
before the first stage of an infected revision but not before reim-
plantation. We might have a wrong approach when we attempt to
develop a single definition suitable for all situations. Further
investigation is definitively warranted. Lastly, the art of establishing
a differential diagnosis using the signs and symptoms during the
evaluation of history and physical should also be considered. The
judicious collection of those tests that make part of the 2013 ICM
definition and alpha-defensin is highly suggested concerning the
diagnosis of PJI.
References
[1] Kurtz SM, Lau E, Watson H, Schmier JK, Parvizi J. Economic Burden of peri-
prosthetic joint infection in the United States. J Arthroplasty 2012;27:
61e65.e1. https://doi.org/10.1016/j.arth.2012.02.022.
[2] Parvizi J, Zmistowski B, Berbari E, Bauer T, Springer B, Della Valle C, et al. New
definition for periprosthetic joint infection: from the workgroup of the
musculoskeletal infection society. Clin Orthop Relat Res 2011;469:2992e4.
https://doi.org/10.1007/s11999-016-5088-5.
[3] Parvizi J, Gehrke T. Definition of periprosthetic joint infection. J Arthroplasty
2014;29:1331. https://doi.org/10.1016/j.arth.2014.03.009.
[4] Osmon DR, Berbari EF, Berendt AR, Lew D, Zimmerli W, Steckelberg JM, et al.
Diagnosis and management of prosthetic joint infection: clinical practice
guidelines by the infectious Diseases society of America. Clin Infect Dis
2013;56:1e25. https://doi.org/10.1093/cid/cis803.
[5] Parvizi J, Tan TL, Goswami K, Higuera C, Della Valle C, Chen AF, et al. The 2018
definition of periprosthetic hip and knee Infection : an evidence-based and
validated criteria. J Arthroplasty 2019;33:1309e1314.e2. https://doi.org/
10.1016/j.arth.2018.02.078.
[6] Saleh A, Ramanathan D, Siqueira MBP, Klika AK, Barsoum WK, Higuera
Rueda CA. The diagnostic utility of synovial fluid markers in periprosthetic
joint Infection : a systematic review and meta-analysis. J Am Acad Orthop Surg
2017;25:763e72. https://doi.org/10.5435/JAAOS-D-16-00548.
[7] Shohat N, Bauer T, Buttaro M, Budhiparama N, Cashman J, Della Valle CJ,
et al. Hip and knee section, what is the definition of a periprosthetic
joint infection (PJI) of the knee and the hip? Can the same criteria be
used for both joints?: proceedings of international consensus on ortho-
pedic infections. J Arthroplasty 2019;34:S325e7. https://doi.org/10.1016/
j.arth.2018.09.045.
[8] Wyles CC, Larson DR, Houdek MT, Sierra RJ, Trousdale RT. Utility of synovial
fluid aspirations in failed metal-on-metal total hip arthroplasty. J Arthroplasty
2019;28:818e23. https://doi.org/10.1016/j.arth.2012.11.006.
[9] Wyles C, Van Demark III RE, Sierra RJ, Trousdale RT. High rate of infection after
aseptic revision of failed metal-on-metal total hip arthroplasty. Clin Infect Dis
2014;472:509e16. https://doi.org/10.1007/s11999-013-3157-6.
[10] Judd KT, Noiseux N. Concomitant infection and local metal reaction in patients
undergoing revision of metal on metal total hip arthroplasty. Iowa Orthop J
2011;31:59e63.
[11] George J, Kwiecien G, Klika AK, Ramanathan D, Bauer TW, Barsoum WK, et al.
Are frozen sections and MSIS criteria reliable at the time of reimplantation of
two-stage revision Arthroplasty ? Clin Orthop Relat Res 2016;474:1619e26.
https://doi.org/10.1007/s11999-015-4673-3.
[12] Frangiamore SJ, Siqueira MBP, Saleh A, Daly T, Higuera CA, Barsoum WK.
Synovial cytokines and the MSIS criteria are not useful for determining
infection resolution after periprosthetic joint infection explantation. Clin
Orthop Relat Res 2016;474:1630e9. https://doi.org/10.1007/s11999-016-
4710-x.
[13] Diaz-Ledezma C, Higuera CA, Parvizi J. Success after treatment of peri-
prosthetic joint Infection : a delphi-based international multidisciplinary
consensus. Clin Orthop Relat Res 2013;471:2374e82. https://doi.org/10.1007/
s11999-013-2866-1.
[14] Kheir MM, Ackerman CT, Tan TL, Benazzo A, Tischler EH, Parvizi J. Leukocyte
esterase strip test can predict subsequent failure following reimplantation in
patients with periprosthetic joint infection. J Arthroplasty 2019;32:1976e9.
https://doi.org/10.1016/j.arth.2017.01.031.
[15] Samuel LT, Sultan AA, Kheir M, Villa J, Patel P, Parvizi J, et al. Positive alpha-
defensin at reimplantation of a two-stage revision arthroplasty is not asso-
ciated with infection at 1 year. Clin Orthop Relat Res 2019;477:1615e21.
https://doi.org/10.1097/CORR.0000000000000620.
 J.M. Villa et al. / The Journal of Arthroplasty 35 (2020) S9eS13
[16] Tsaras G, Maduka-Ezeh A, Inwards CY, Mabry T, Erwin PJ, Murad HM, et al.
Utility of intraoperative frozen section histopathology in the diagnosis of
periprosthetic joint infection: a systematic review and meta-analysis. J Bone
Joint Surg Am 2012;94:1700e11.
[17] Kwiecien G, George J, Klika AK, Zhang Y, Bauer TW, Higuera Rueda CA.
Intraoperative frozen section Histology : matched for musculoskeletal infec-
tion society criteria. J Arthroplasty 2019;32:223e7. https://doi.org/10.1016/
j.arth.2016.06.019.
[18] Gehrke T, Lausmann C, Citak M, Bonanzinga T, Frommelt L, Zahar A. The ac-
curacy of the alpha defensin lateral flow test for diagnosis of periprosthetic
joint infection. J Bone Joint Surg Am 2018;100:42e8. https://doi.org/10.2106/
JBJS.16.01522.
S13
[19] Renz N, Yermak K, Perka C, Trampuz A. Alpha defensin lateral flow test for
diagnosis of periprosthetic joint infection. J Bone Joint Surg Am 2018;100:
742e50. https://doi.org/10.2106/JBJS.17.01005.
[20] Shahi A, Kheir MM, Tarabichi M, Hosseinzadeh HRS, Tan TL, Parvizi J. Serum D-
dimer test is promising for the diagnosis of periprosthetic joint infection and
timing of reimplantation. J Bone Joint Surg Am 2017;99:1419e27.
[21] Li R, Shao H-Y, Hao L-B, Yu B-Z, Qu P-F, Zhou Y-X, et al. Plasma fibrinogen exhibits
better performance than plasma D-dimer in the diagnosis of periprosthetic joint
infection: a multicenter retrospective study. J Bone Joint Surg Am 2019;101:613e9.
[22] Xu H, Xie J, Huang Q, Lei Y, Zhang S, Pei F. Plasma fibrin degradation product
and D-dimer are of limited value for diagnosing periprosthetic joint infection.
J Arthroplasty 2019;34:2454e60. https://doi.org/10.1016/j.arth.2019.05.009.