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20 Low-Grade Periprosthetic Infections
303
Orthop Relat Res. 2012;470(5):1461–71. Available
from: https://pubmed.ncbi.nlm.nih.gov/22081299/.
43. Kunutsor SK, Beswick AD, Whitehouse MR, Wylde
V, Blom AW. Debridement, antibiotics and implant
retention for periprosthetic joint infections: a systematic review and meta-analysis of treatment outcomes.
J Infect. 2018;77(6):479–88. Available from: https://
pubmed.ncbi.nlm.nih.gov/30205122/.
44. Malahias MA, Gu A, Harris EC, Adriani M, Miller
AO, Westrich GH, etal. The role of long-term antibiotic suppression in the management of peri-prosthetic joint infections treated with debridement,
antibiotics, and implant retention: a systematic
review. J Arthroplasty. 2020;35(4):1154–60.
Available from: https://pubmed.ncbi.nlm.nih.
gov/31955984/.
45. Kurd MF, Ghanem E, Steinbrecher J, Parvizi J.Twostage exchange knee arthroplasty: does resistance of
the infecting organism inuence the outcome? Clin
Orthop Relat Res. 2010;468(8):2060–6. Available
from: https://pubmed.ncbi.nlm.nih.gov/20300903/.
46. Darwich A, Dally FJ, Olba KA, Mohs E, Gravius
S, Hetjens S, et al. Superinfection with difcult-totreat pathogens signicantly reduces the outcome of
periprosthetic joint infections. Antibiotics (Basel).
2021;10(10). Available from: https://pubmed.ncbi.
nlm.nih.gov/34680726/
47. Cordero-Ampuero J, Esteban J, García-Rey
E. Results after late polymicrobial, gram-negative,
and methicillin- resistant infections in knee arthroplasty. Clin Orthop Relat Res. 2010;468(5):1229–36.
Available from: https://pubmed.ncbi.nlm.nih.
gov/20087702/.
48. Nelson GN, Davis DE, Namdari S.Outcomes in the
treatment of periprosthetic joint infection after shoulder arthroplasty: a systematic review. J Shoulder
Elbow Surg. 2016;25(8):1337–45. Available from:
https://pubmed.ncbi.nlm.nih.gov/27012542/.
What Is New inPeriprosthetic Joint
Infection After Hip andKnee
Arthroplasty
ShayanHosseinzadeh, JesusVilla,
andCarlosHiguera
21
21.1 Introduction
Periprosthetic joint infection (PJI) is a devastating complication following hip and knee arthroplasty, causing signicant morbidity and
mortality. Despite advances, PJI remains a challenging problem in orthopedics mainly due to the
lack of understanding of physiopathology [1].
This chapter discusses recent developments in
PJI’s understanding and management.
PJI’s clinical signicance stems from increasing joint replacements, an aging population, and
related comorbidities like obesity and diabetes. It
poses serious health and economic challenges,
with projected annual hospital costs of $1.85 billion by 2030in the USA.Urgent preventive strategies are needed to address this issue and combat
antibiotic-resistant pathogens [2, 3].
To address healthcare-associated infections,
research has explored antiseptics, antimicrobial
sutures, and extended oral antibiotic prophylaxis
[4, 5]. Intraosseous regional administration of
antibiotics has also shown potential for enhancing prevention, and treatment outcomes [6].
Advances in PJI diagnosis involve nextgeneration sequencing, metagenomic sequencing, and various biomarkers like leucocyte
S. Hosseinzadeh · J. Villa · C. Higuera (*)
Levitetz Department of Orthopaedic Surgery,
Cleveland Clinic Florida. 2950 Cleveland Clinic
Blvd, Weston, FL, USA
e-mail: higuerc@ccf.org
esterase, calprotectin, serum D-dimer, and
immune checkpoint molecules, leading to faster
and more accurate identication of pathogens
[7–16].
Treatment approaches include debridement
and antibiotics with implant retention (DAIR),
two-stage, one-stage, and one-and-a-half-stage
revision arthroplasty, with each having benets
and considerations [17, 18].
In summary, recent developments emphasize
a comprehensive approach to PJI, focusing on
prevention, improved diagnostics, and customized treatments to enhance patient outcomes [19].
21.2 Etiology andRisk Factors
21.2.1 Novel Insights into PJI
Microbiology
Recent research has expanded our understanding
of PJI, traditionally linked to bacterial pathogens
like Staph aureus and coagulase-negative staphy-
lococci. New evidence suggests the involvement
of previously overlooked microorganisms,
including fungi and mycobacteria, broadening
the understanding of PJI’s etiology. Polymicrobial
infections and anaerobic bacteria are sometimes
associated with atypical presentations and diagnostic challenges. A study comparing PJI organisms in different nations revealed variations in
the type of microorganisms and increased overall
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2025
P. Ruggieri et al. (eds.), Bone and Joint Infections, https://doi.org/10.1007/978-3-031-96383-4_21
305
306
S. Hosseinzadeh et al.
incidence of resistant bacteria. Next-generation
sequencing techniques have signicantly
enhanced the detection of bacterial lineages
within clinical specimens, particularly in the context of polymicrobial infections, where E. coli, C.
acnes, S. epidermidis, and S. aureus are commonly identied as the predominant organisms.
However, the sensitivity of next-generation
sequencing for bacterial detection may lead to
the identication of contaminants, necessitating
careful interpretation of the results. Investigating
the baseline microbial signal enhances clinical
translation and understanding of PJI’s microbial
changes during joint infections or prosthesis failure [20–22].
21.2.2 Advancements inIdentifying
Host Risk Factors
Recent studies have shed light on host risk factors
associated with PJI, providing a deeper understanding of the risks faced by joint arthroplasty
patients. Obesity has been identied as an independent risk factor due to its impact on inammatory responses and increased adipose tissue,
with patients having a BMI greater than 40 facing
a three-fold higher risk of PJI compared to those
with lower BMI values. Various techniques have
been developed to assess local adiposity in the
knee joint, including the ratio of the prepatellar
thickness (PPT) to the thickness of the patella,
the measurement of both PPT and pretubercular
thickness, and the determination of the soft
tissue- to-bone ratio in lateral knee radiographs.
These specic assessments of local knee adiposity have demonstrated associations with the risk
of PJI following TKA.Nevertheless, the collective evidence indicates that BMI serves as a superior predictor of PJI occurrence after TKA when
compared to localized measurements of knee adipose tissue [23].
Additionally, systemic conditions, such as
diabetes mellitus, rheumatoid arthritis, and
chronic kidney disease, have shown an elevated
likelihood of PJI following joint arthroplasty,
with patients with diabetes carrying a 1.7-fold
greater risk. Elevated HbA1c levels have demon-
strated a clear association with an increased risk
of PJI.Notably, a threshold of 7.7% appears to
provide a more accurate indicator of infection
risk compared to the commonly utilized 7%.
Therefore, it may be prudent to set 7.7% as the
target HbA1c level during preoperative patient
optimization [24]. In addition to HbA1c, fructosamine emerges as another valuable predictor of
complications following TKA. Fructosamine
offers several advantages, including a more precise reection of glycemic control, enhanced predictive capacity for adverse events, and quicker
responsiveness to treatment when compared to
HbA1c. Recent research ndings strongly
endorse the inclusion of fructosamine screening
for all patients undergoing TKA.For individuals
with fructosamine levels exceeding 293μmol/l, it
is imperative to conduct a comprehensive riskbenet analysis prior to considering surgery.
Optimizing glycemic control becomes paramount as a prerequisite for proceeding with the
surgical intervention [25].
Immunocompromised individuals receiving
long-term corticosteroid therapy, immunotherapy, or chemotherapy face heightened risks due
to compromised immune defenses, highlighting
the need for vigilant monitoring and additional
optimization in these cases. Both the American
College of Rheumatology and the American
Association of Hip and Knee Surgeons guidelines provide recommendations for managing
these patients [26].
Furthermore, smoking and malnutrition are
increasingly recognized as modiable risk factors, with smoking contributing to a 3.5-fold
higher risk of PJI in patients with obesity. It has
also been shown that individuals who currently
smoke face a markedly heightened risk of requiring reoperation for infection within 90days following a surgical procedure when compared to
their non-smoking counterparts. Additionally, it
has been proven that the cumulative lifetime consumption of cigarettes, irrespective of one’s present smoking status, substantially contributes to
an elevated risk of nonoperative readmission
[27]. As a result, it is advisable for patients to try
to cease smoking at least 2–3weeks before the
scheduled procedure.
21 What Is New inPeriprosthetic Joint Infection After Hip andKnee Arthroplasty
307
21.3 Prevention ofPJI: Recent
Advancements andNovel
Strategies
Healthcare-associated infections, particularly
surgical site infections (SSIs), continue to pose
signicant challenges despite efforts to combat
antibiotic-resistant pathogens and enforce guidelines. In response to this concern, studies have
investigated innovative approaches to preventing
SSI without solely relying on antibiotics. Its discussions have centered around the use of antiseptics and antimicrobial sutures in surgical practice.
A broader implementation of antiseptics has also
been proposed to reduce the reliance on antibiotics for infection prevention, encompassing preoperative measures such as showering, hand
hygiene, and skin preparation, along with postoperative wound management. Additionally, there
is growing support for the use of antimicrobial
sutures in high-risk procedures and cases where
SSI could be life-threatening despite low occurrence rates [4].
The introduction of chlorhexidineimpregnated wipes or soap in the presurgical
environment has had mixed results in the reduction of SSI incidence [28, 29], however, in our
practice, we have noted an effect on SSI reduction, and for that reason, we continue its use. We
usually prescribe a chlorhexidine solution to be
used at least the day before and the day of the
procedure, mainly in the surgical area. It has also
been demonstrated that both single and 24-h antibiotic dosages are equally effective in preventing
PJI in TJA.Therefore, the use of a single antibiotic dose can be safely considered for patients
undergoing routine primary TJA [30].
Furthermore, studies indicate that administering
additional antibiotics after skin closure may not
be necessary for primary TJA, irrespective of the
patient’s preoperative risk of PJI [31].
Recent research studies have investigated the
effects of extended oral antibiotic prophylaxis
(EOA) on infection-related outcomes following
primary and revision surgeries for TKA and
THA. The ndings of these investigations suggest that employing EOA prophylaxis can effectively reduce the incidence of PJI among high-risk
primary and revision THA and TKA patients
[32–34].
Meanwhile, the use of intraosseous regional
administration (IORA) of antibiotics has emerged
as a novel technique for delivering antibiotics
directly to the surgical site in patients undergoing
TKA and THA.This approach involves administering antibiotics into the bone leading to higher
local tissue concentrations of antibiotics [6, 35].
A comprehensive analysis was undertaken to
evaluate the efcacy of IORA, focusing on studies reporting on perioperative prophylaxis during
TKA.The analysis included eight studies, with
four of them being randomized controlled trials
comparing local tissue antibiotic concentrations
between patients receiving IORA and those
receiving intravenous (IV) antibiotics.
Additionally, six studies assessed the rate of PJI
among patients receiving IORA versus IV antibiotics [6]. The combined ndings from these studies consistently indicated a signicant increase in
antibiotic concentration in femoral bone and fat
samples among patients treated with
IORA. Notably, the tissue concentrations
achieved with IORA were, on average, 10 times
higher than those achieved with IV administration alone. For example, after the administration
of 500mg of intraosseous vancomycin, the antibiotic concentrations in fat and bone samples
were 44.04 μg/g and 49.3 μg/g, respectively,
compared to 3.5μg/g (fat) and 5.2 μg/g (bone)
following 1g IV of vancomycin [6].
Moreover, the results of two adequately powered studies demonstrated a statistically signicant decrease in the rate of PJI among patients
receiving IORA compared to those receiving IV
antibiotics. The overall incidence of PJI in
patients treated with IORA was only 0.3%, while
it was 1.1% in patients receiving IV antibiotics
across all studies [6].
The use of topical vancomycin powder (VP)
in joint replacement surgeries has become popular due to positive outcomes in spinal surgery
[36] and open fracture treatment [37]. However,
it can contribute to antibiotic resistance.
Understanding VP’s behavior in synovial uid is
limited [38], particularly its potential to create
wear between joint components. Yet, VP does not
308
S. Hosseinzadeh et al.
seem to affect wear between ultra-highmolecular- weight polyethylene (UHMWP) and
cobalt-chrome alloy (CoCr) [39]. Reviews on VP
in hip and knee arthroplasty yield conicting
results, mostly based on lower-level evidence
with confounding factors. Currently, there’s
insufcient data to recommend routine VP use in
these surgeries [40]. A well-powered randomized
trial is needed to clarify its role. VP seems safe in
terms of systemic side effects, and if its efcacy
can be established, it could offer cost-effective
benets [40].
Povidone-iodine (PI) effectively eliminates
methicillin-resistant Staphylococcus aureus
(MRSA) within 30s [41]. In primary TKA and
THA, a diluted 0.35% PI lavage before wound
closure reduced postoperative prosthetic infections from 0.97% to 0.15% [42]. However, not all
studies support PI’s use [43, 44]. While efcacy
reports vary, it’s a cost-effective, low-risk option.
Several organizations, including the 2017
International Consensus Meeting Clinical
Practice Guidelines, endorse PI lavage before
closure to prevent infection [45–47].
In a recently updated randomized clinical
trial involving patients who underwent knee or
hip arthroplasty, researchers found that aspirin
prophylaxis demonstrated comparable efcacy
and safety outcomes when compared to other
anticoagulants. Furthermore, when compared to
a placebo, aspirin prophylaxis showed a signicant reduction in venous thromboembolism
(VTE) risk while maintaining a similar safety
outcome [48]. There is newer evidence that the
use of aspirin instead of other anticoagulants to
prevent VTE is correlated with a lower incidence
of SSI [49].
In a comprehensive meta-analysis, the
Grading of Recommendations, Assessment,
Development, and Evaluations (GRADE)
revealed high- certainty evidence supporting the
prophylactic application of negative pressure
wound therapy on primary closed incisional
wounds for the prevention of surgical site infections. Furthermore, this analysis suggested
reduced uncertainty compared to earlier metaanalyses. Additionally, the trial sequential analysis performed suggested that additional trials are
unlikely to alter the estimated effect of incisional
negative pressure wound therapy on the prevention of surgical site infections [50]. A multicenter randomized study showed that the risk of
reoperations is also lower when this technology
is used in high-risk patients [51].
Anti-glucosaminidase (GMD) immunization:
A recent study indicated higher levels of endogenous anti-Gmd antibodies in patients’ sera correlate with better infection control rates and
lower adverse outcomes in S. aureus bone infec-
tions. This suggests the potential benet of
exploring GMD immunization as a strategy for
improving treatment outcomes in osteomyelitis
[52]. It is a probability that in the future we may
have vaccines available to prevent PJI.
In a recent cohort study involving 9427 cases
of late prosthetic joint infections, no compelling
evidence was discovered to establish a temporal
link between invasive dental procedures and PJIs.
Consequently, these ndings challenged the prevailing recommendations advocating for antibiotic prophylaxis administration to patients with
prosthetic joints before undergoing invasive dental procedures. This challenge stemmed from
cost concerns, the potential for adverse drug
reactions, and the associated risk of inducing
antibiotic resistance, all of which are linked to
antibiotic prophylaxis [53].
In a comparable scenario, research has also
indicated that administering antibiotic prophylaxis does not reduce the risk of PJI in individuals
who have undergone TJA when they undergo
colonoscopy. When adjusting for established risk
factors, it was observed that TJA recipients
undergoing colonoscopy, both with and without
antibiotic prophylaxis, exhibited similar PJI risks
in comparison to a control group that did not
undergo colonoscopy. However, it is important to
note that individuals with a history of alcohol
abuse, diabetes, or rheumatoid arthritis experienced a greater risk of PJI when undergoing colonoscopy after TJA compared to those who did not
have colonoscopies. Therefore, the ndings suggest that for most TJA patients undergoing colonoscopy, the use of antibiotics may not be
necessary, except for those individuals with these
high-risk factors [54].
21 What Is New inPeriprosthetic Joint Infection After Hip andKnee Arthroplasty
309
21.4 Diagnosis ofPJI: Recent
Advances andApproaches
The diagnosis of PJI relies on a combination of
clinical criteria and diagnostic markers. Elevated
serum C-reactive protein (CRP), D-dimer, and
erythrocyte sedimentation rate (ESR), along with
various synovial uid parameters, are commonly
investigated. Intraoperative ndings, such as frozen section analysis, the presence of purulence,
and pathogen isolation by culture, also play a
crucial role in conrming the diagnosis.
To establish infection status, a scoring system
is employed based on the diagnostic markers. An
elevated serum CRP (>1 mg/dL), D-dimer
(>860 ng/mL), and ESR (>30 mm/h) receive
assigned points of 2, 2, and 1, respectively.
Similarly, elevated synovial uid white blood cell
count (>3000 cells/μL), alpha-defensin (signalto- cutoff ratio>1), leukocyte esterase (++), polymorphonuclear percentage (>80%), and synovial
CRP (>6.9mg/L) are assigned points of 3, 3, 3, 2,
and 1, respectively. A total aggregate score of 6 or
higher indicates a PJI diagnosis, while scores
between 2 and 5 necessitate consideration of
intraoperative ndings for conrmation or refutation. Intraoperative ndings such as positive histology, presence of purulence, and single positive
culture are assigned points of 3, 3, and 2, respectively. When combined with the preoperative
score, a total score of 6 or higher conrms infection, a score between 4 and 5 remains inconclusive, and a score of 3 or less rules out infection.
This updated evidence-based approach for diagnosing hip and knee PJI demonstrates higher sensitivity (97.7%) compared to the older MSIS
(79.3%) and International Consensus Meeting
denitions (86.9%), while maintaining a similar
specicity of 99.5%. These rened diagnostic
criteria enable more accurate identication of
PJI, facilitating timely and targeted treatment
interventions [7].
The reported incidence of culture-negative PJI
in the hip or knee varies between 7% and 42%,
yielding an overall estimated incidence rate of
11% utilizing a random-effects model [55].
Recent ndings indicate that the semiautomated
periprosthetic tissue culture method using blood
culture bottles exhibits greater sensitivity and
comparable specicity when compared to agar
and thioglycolate broth cultures, while also delivering faster results [56].
The leucocyte esterase (LE) strip test has
gained recognition as a valuable biomarker for
PJI diagnosis. This test detects the presence of
leukocyte esterase, an enzyme released by white
blood cells, in synovial uid. It offers convenience, speed, and immediate results, making it a
promising option in the diagnostic workup for
PJI. However, the LE strip test has limitations,
such as imprecision and susceptibility to interference mainly on bloody aspirations. To address
these limitations, new technologies, including
machine reading, quantitative detection, and articial intelligence, are being applied to enhance
the accuracy of the LE strips test. These advancements aim to improve its precision and minimize
potential sources of interference, ultimately
improving its diagnostic accuracy [10]. Alphadefensin is another promising synovial biomarker
with encouraging results. Its utilization as a diagnostic marker alongside synovial white cell
count, culture bacteriology, and other biomarkers
is particularly valuable, especially in complex
PJI diagnostic scenarios [11]. Another biomarker
that has shown promise in PJI diagnosis is calprotectin. The calprotectin point-of-care (POC)
test has demonstrated excellent diagnostic characteristics, including high sensitivity and specicity, particularly in patients undergoing revision
TKA.The calprotectin POC test can effectively
serve as a rule-out test, helping to exclude PJI
when the results are negative. With its rapid and
reliable results, the calprotectin POC test contributes to more efcient management of patients
where PJI is suspected [12].
Furthermore, recent research has evaluated
immune checkpoint molecules as potential predictors of PJI. Periprosthetic joint infections
induce an immunosuppressive cytokine prole
through an unknown mechanism. Immune checkpoints, like programmed cell death 1 (PD-1) and
its ligand (PD-L1), initiate innate immunosuppressive pathways essential for self-tolerance.
Several malignancies and chronic infections coopt these pathways to derive a survival advantage.
310
S. Hosseinzadeh et al.
In a study evaluating PD-1/PD-L1 expression in
periprosthetic tissue from patients undergoing
revision hip or knee arthroplasty for PJI versus
aseptic failure, PD-1/PD-L1 expression was analyzed using immunohistochemistry. The results
of this study supported immune checkpoint
upregulation as a mechanism of PJI- induced
local immune dysfunction. Further studies are
needed to conrm PD-L1 as a risk factor for reinfection in larger cohorts [13, 14].
In parallel, the effectiveness of the D-Dimer as
a new diagnostic tool for PJI has been explored
through two distinct studies, each offering unique
insights into its diagnostic performance. These
studies, conducted by Pannu et al. [15] and
Tarabichi et al. [16], contribute to the ongoing
discussions surrounding the utility of D-Dimer in
distinguishing between septic and aseptic revisions in patients undergoing revision total hip
and knee arthroplasty.
In the retrospective review undertaken by
Pannu etal., the researchers analyzed a cohort of
143 patients who had undergone revision total
hip and knee arthroplasties with preoperative
D-Dimer orders. The central focus was on differentiating cases with low-virulence (LV) and
high-virulence (HV) organisms. The results
revealed that despite its potential sensitivity in
detecting PJI cases with LV organisms—cases
that are often difcult to diagnose using conventional methods—the overall accuracy of D-Dimer
was disappointingly low, at around 57%. This
suggests that while D-Dimer might excel in identifying certain specic cases of PJI, its general
diagnostic performance in distinguishing septic
from aseptic revisions fell short of expectations.
Nonetheless, the study highlights the potential of
D-Dimer as a viable option for cases that tend to
be overlooked by traditional diagnostic techniques [15].
On the other hand, the prospective study led
by Tarabichi etal. involved a larger sample size
of 502 patients who were undergoing revision hip
or knee arthroplasty. Their ndings painted a
more optimistic picture of D-Dimer’s diagnostic
capabilities. In this study, D-Dimer’s diagnostic
utility for PJI was compared to other commonly
used biomarkers, such as serum CRP and
ESR.The results suggested that plasma D-Dimer
demonstrated diagnostic performance on par
with these established biomarkers. This points to
the potential of D-Dimer to serve as a valuable
adjunct in the screening process for patients
undergoing revision total joint arthroplasty. By
demonstrating comparable diagnostic efcacy to
established markers, D-Dimer’s inclusion in the
diagnostic toolkit could potentially enhance the
accuracy of identifying PJI cases [16].
Next-generation sequencing (NGS) is a powerful molecular technique that has emerged as a
valuable tool in the diagnosis of PJI.It involves
the parallel sequencing of DNA fragments in a
sample, allowing for the identication of various
microorganisms. Recent advancements in NGS
have made it more routine and cost-effective
especially in cases where the cultures have been
negative [8]. Metagenomic next-generation
sequencing (mNGS) is a specic application of
NGS that has revolutionized the eld of infectious disease diagnostics. It detects the entire
DNA or RNA sequence in a sample, enabling the
identication of pathogens, including bacteria,
viruses, fungi, and parasites, within 24–48 h.
This is signicantly faster compared to traditional bacterial culture methods, which can take
several days to identify bacteria in synovial uid.
mNGS is particularly valuable in cases where
there is a strong suspicion of PJI but conventional
diagnostic tests, such as cultures, yield negative
results [9].
New evidence on MRI sequences such as
MAVRIC has demonstrated that magnetic resonance imaging using MAVRIC is a highly specic diagnostic tool for detecting PJI with a
minimal false-positive rate. This suggests that
when healthcare providers encounter an MRI
result that unexpectedly indicates infection, it
warrants a formal assessment for the presence of
infection. In cases where diagnostic results are
inconclusive, MRI may serve as a valuable tool to
support the diagnosis and potentially the treatment of PJI, although it may not denitively rule
it out [57].
Lastly, combining labeled-leucocyte imaging
(e.g., leucocytes labeled with indium-111) with
bone marrow imaging utilizing
21 What Is New inPeriprosthetic Joint Infection After Hip andKnee Arthroplasty
311
technetium- 99m-labeled sulfur colloid proves to
be more accurate in detecting infections associated with prosthetic joints than technetium-99
imaging alone, a combination of bone and gallium-67 imaging, or labeled-leucocyte and bone
imaging. When compared directly, this combination stands as the preferred choice for an imaging
scan when infection assessment is necessary
[58].
21.5 Treatment ofPJI: Recent
Advances andStrategies
21.5.1 Multidisciplinary Approach
The management of PJI requires a multidisciplinary approach involving orthopedic surgeons,
infectious disease specialists, microbiologists,
and other healthcare professionals. Collaboration
between these experts is crucial to developing an
individualized treatment plan tailored to the
patient’s specic circumstances [19, 59].
21.5.2 Surgical Strategies
Recent advancements have focused on rening
surgical strategies to improve outcomes in PJI
treatment.
21.5.2.1 Debridement andAntibiotics
andImplant Retention (DAIR)
DAIR is an effective treatment for acute postoperative or hematogenous PJI in an appropriately selected patient with well-xed implants.
Over the last two decades, signicant progress
has been made in this eld. While denitively
determining which of these improvements has
been the most efcacious remains a challenge,
one of the most notable advancements has been
the recognition of the critical importance of
meticulous and aggressive debridement techniques. Furthermore, there has been a growing
adoption of antimicrobial irrigation, which may
also contribute to reducing infection risk,
though the available evidence is somewhat
mixed [60].
Another substantial innovation has been the
introduction of intraosseous vancomycin [61].
This method has proven to be both safe and effective in providing antibiotic prophylaxis while
minimizing the systemic side effects associated
with vancomycin. Emerging evidence has demonstrated safety along with enhanced outcomes
when contrasted with earlier studies utilizing
conventional DAIR methods without intraosseous antibiotic delivery, although further data is
still needed for conrmation [62].
Additionally, a more recent technique known
as “Double DAIR” has emerged, offering
improved solutions to address the limitations of a
single-stage DAIR procedure. Initial results from
“Double DAIR” procedures have shown promising success in managing infections [63].
21.5.2.2 Two-Stage Revision
Arthroplasty
Two-stage exchange arthroplasty is the preferred
treatment for chronic PJI in the United States. It
involves two surgeries with a time interval
between them. In the rst stage, the prosthesis is
removed, the area is thoroughly cleaned and
treated with antibiotics, and an antibiotic-eluting
cement spacer is inserted to maintain joint space
and motion. Articulating spacers generally offer
better outcomes, while static spacers are preferred for certain conditions like ligamentous
instability, widespread bone loss, or signicant
soft tissue defects. Cultures and preoperative
work-ups are crucial, and prophylactic antibiotics are given before incision. The duration of
antibiotic therapy for patients with PJI is primarily based on expert recommendations rather than
evidence. Patients usually receive long courses of
antibiotic therapy, which can take up to 6months
for staph infections [17]. Several studies suggest
that shorter courses may be adequate for most
cases of PJI and that they may be associated with
shorter hospital stays, fewer side effects, and the
establishment of microbiologic resistance.
However, recent prospective randomized noninferiority research compared a 6-week course of
antibiotic treatment to a 12-week course and
found that antibiotic therapy for 6weeks resulted
in a larger percentage of patients with poor
312
S. Hosseinzadeh et al.
outcomes [64]. There’s also debate about the
need for a 2-week antibiotic-free period before
reimplantation [17].
Conrming infection control before reimplantation is vital, but the available criteria have limitations. The decision for reimplantation is
complex and may involve various tests, including
cultures. Unfortunately, there is no denitive
marker that establishes absolute infection control
[65]. It is also worth mentioning that plasma
D-dimer levels paradoxically increase prior to
reimplantation, while other inammatory markers such as ESR and CRP decrease, which
emphasizes the importance of exercising caution
when incorporating D-dimer into clinical
decision- making by surgeons [66]. Moreover,
there is a lack of consensus regarding the necessity of aspiration prior to reimplantation, with
conicting data on this matter.
After conrming infection control, the second
stage involves removing the cement spacer and
reimplanting the new prosthesis. Two-stage revision is suitable for patients with more challenging infections and bone deciencies. It has
drawbacks like increased cost and higher morbidity. In some cases, patients may choose to retain
the spacer instead of proceeding with the second
stage, which has shown acceptable results in
selected cases [17].
21.5.2.3 One-Stage Revision
Arthroplasty
One-stage revision arthroplasty is an alternative
to two-stage revision for PJI. While two-stage
revision is standard, it has a 26% mortality rate at
5years [67]. In contrast, one-stage revision offers
comparable reinfection rates and better functional outcomes.
Strict selection criteria include moderate bone
loss, no immunocompromising conditions,
healthy soft tissues, known organisms with antibiotic sensitivities, and favorable immune status.
Notably, while 6.7% of two-stage patients experienced reinfection 3 years postoperatively in a
study by Haddal et al., not a single one-stage
patient experienced recurrent infection [68].
One-stage revision showed high success rates for
both hip and knee revisions [17].
Choosing the right procedure at presentation
is crucial, as the success of repeated revisions
decreases over time [68]. One-stage revision
should be considered for PJI patients meeting
such strict criteria.
21.5.2.4 One-and-a-Half Stage
Revision Arthroplasty
The 1.5-stage revision TKA is a promising alternative that involves the use of a prosthetic articulating spacer, preserving knee function, and
potentially delaying the need for a second surgery indenitely. This technique has shown an
85% infection-free survival rate after nearly
3years [69]. The procedure involves the resection of infected TKA components, thorough
debridement, and implantation of revision components in a single surgery.
Key surgical considerations include meticulous debridement with a focus on preserving collateral ligaments, assessing techniques for
restoring the joint line, and ensuring precise
placement of the femoral component. It is crucial
to properly evaluate bone loss, use augmentations when necessary, and be meticulous during
the cementing process, and avoid common pitfalls such as rushing component removal [70].
Overall, the 1.5-stage revision TKA is a viable
option for treating chronic PJI in TKA, offering
advantages such as reduced costs and improved
patient outcomes. Further studies are needed to
determine its broader applicability and indications, but it has been successful in providing
excellent knee function and avoiding the urgency
of planning for the next revision surgery. If ever
needed in the future, this procedure can be scheduled more electively, providing patients with
greater exibility and peace of mind [71–74].
21.5.3 Other Therapeutic Strategies
In one study, researchers explored whether a
3-month course of oral antibiotics could reduce
the risk of infection-related failure following a
two-stage joint replacement procedure. Results
showed that patients treated with oral antibiotics
experienced a signicantly lower failure rate due
21 What Is New inPeriprosthetic Joint Infection After Hip andKnee Arthroplasty
313
to infection compared to those without antibiotics
(5% vs. 19%). However, some patients encountered adverse reactions to antibiotics, and issues
related to adherence were observed. Further follow-up is necessary to conrm the long-term efcacy and safety of this approach [5].
Recent research demonstrated that PlySs2, a
bacteriophage-derived lysin, is more effective
than vancomycin in reducing S. aureus biolm
and colony-forming units on orthopedic implants.
When combined with vancomycin, PlySs2 signicantly reduces the bacterial load on implant
surfaces and in periprosthetic tissue. This highlights the potential of lysins to enhance the treatment of prosthetic joint infections caused by S.
aureus biolms [75, 76].
Other recent studies emphasize the potential
of phage therapy as a promising approach to
treating prosthetic joint infections. Phages have
the ability to degrade biolms and target bacterial
cells, working synergistically with antibiotics.
They can be personalized to target specic bacterial strains. However, more research is needed to
optimize delivery methods and understand
phage-host interactions to ensure successful
translation into clinical practice [77–79].
WLBU2, an engineered peptide, demonstrates
effectiveness in removing S. aureus biolms on surgical implants. It effectively treats biolms formed
by various clinical strains and leads to culture-negative implants. WLBU2 shows rapid elimination of
implants invitro and has sufcient efcacy invivo
with minimal systemic toxicity [80, 81].
TRL1068, a fully human antibody, also shows
potential for disrupting biolms formed by grampositive and gram-negative bacteria. It targets a
conserved epitope on DNABII proteins, which
are crucial for biolm formation. The absence of
similar counterparts in human proteins enhances
their therapeutic potential [82–86].
References
1. Mian HM, Lyons JG, Perrin J, Froehle AW,
Krishnamurthy AB.A review of current practices in
periprosthetic joint infection debridement and revision arthroplasty. Arthroplasty. 2022 Sep 1;4(1):31.
2. Premkumar A, Kolin DA, Farley KX, Wilson JM,
McLawhorn AS, Cross MB, Sculco PK. Projected
economic burden of Periprosthetic joint infection of
the hip and knee in the United States. J Arthroplast.
2021 May;36(5):1484–1489.e3.
3. Urban-Chmiel R, Marek A, Stępień-Pyśniak D,
Wieczorek K, Dec M, Nowaczek A, Osek J.Antibiotic
resistance in bacteria-a review. Antibiotics (Basel).
2022 Aug 9;11(8):1079.
4. Leaper D, Wilson P, Assadian O, Edmiston C, Kiernan
M, Miller A, Bond-Smith G, Yap J.The role of antimicrobial sutures in preventing surgical site infection.
Ann R Coll Surg Engl. 2017 Jul;99(6):439–43.
5. Frank JM, Kayupov E, Moric M, Segreti J, Hansen
E, Hartman C, Okroj K, Belden K, Roslund B,
Silibovsky R, Parvizi J, Della Valle CJ, Knee Society
Research Group. The Mark Coventry, MD, award:
oral antibiotics reduce reinfection after two-stage
exchange: a multicenter, randomized controlled trial.
Clin Orthop Relat Res. 2017 Jan;475(1):56–61.
6. Miltenberg B, Ludwick L, Masood R, Menendez ME,
Moverman MA, Pagani NR, Puzzitiello RN, Smith
EL.Intraosseous regional administration of antibiotic
prophylaxis for total knee arthroplasty: a systematic
review. J Arthroplast. 2023 Apr;38(4):769–74.
7. Parvizi J, Tan TL, Goswami K, Higuera C, Della
Valle C, Chen AF, Shohat N.The 2018 denition of
Periprosthetic hip and knee infection: an evidencebased and validated criteria. J Arthroplast. 2018
May;33(5):1309–1314.e2.
8. Yin H, Xu D, Wang D. Diagnostic value of nextgeneration sequencing to detect periprosthetic joint
infection. BMC Musculoskelet Disord. 2021 Mar
6;22(1):252.
9. Indelli PF, Ghirardelli S, Violante B, Amanatullah
DF.Next generation sequencing for pathogen detection in periprosthetic joint infections. I Open Rev.
2021 Apr 1;6(4):236–44.
10. Chisari E, Yacovelli S, Goswami K, Shohat N,
Woloszyn P, Parvizi J.Leukocyte esterase versus ICM
2018 criteria in the diagnosis of Periprosthetic joint
infection. J Arthroplast. 2021 Aug;36(8):2942–2945.
e1.
11. Bonanzinga T, Ferrari MC, Tanzi G, Vandenbulcke F,
Zahar A, Marcacci M.The role of alpha defensin in
prosthetic joint infection (PJI) diagnosis: a literature
review. I Open Rev. 2019 Jan 23;4(1):10–3.
12. Bottagisio M, Viganò M, Pellegrini A, Logoluso
N, Zagra L, Prina A, de Girolamo L, De Vecchi
E.Evaluation of synovial calprotectin by using a lateral ow test for the diagnosis of prosthetic joint infections. Diagnostics (Basel). 2023 Feb 15;13(4):741.
13. Maimaiti Z, Li Z, Xu C, Fu J, Hao LB, Chen JY, Chai
W. Host immune regulation in implant- associated
infection (IAI): what does the current evidence
provide us to prevent or treat IAI? Bioengineering
(Basel). 2023 Mar 13;10(3):356.
14. Warren SI, Charville GW, Manasherob R,
Amanatullah DF. Immune checkpoint upregulation