Infections in Prosthetic Devic PDF

(N) Infection 06, Ch13 18/7/06 12:57 Page 223
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Infections in prosthetic devices
SUPHA KIJPITTAYARIT, DOUGLAS OSMON, ELIE BERBARI
Introduction
Since prosthetic joint replacement has become a common procedure performed
worldwide, prosthetic joint infection (PJI) has emerged as an important complica-
tion. The current incidence of PJI is 1–2% after joint replacement |1,2|.
The ability to distinguish infection from aseptic loosening is essential because of
the potentially disastrous consequences if the diagnosis is missed or delayed. The
diagnosis of PJI can often be problematic, especially in the case of prosthetic
loosening from chronic low-grade infection. There have been several recent studies
and developments in this area including: proposed criteria for the diagnosis of PJI
using synovial leukocyte count and differential (see Trampuz et al., 2004; reviewed
below), the use of polymerase chain reaction (PCR) on periprosthetic tissue in the
diagnosis of low-grade PJI (see Clarke et al., 2004; and Ince et al., 2004; reviewed
below), and newer techniques such as measurement of interleukin-6 (IL-6) and
evaluation of synovial fluid leukocyte gene expression (see Deirmengian et al.,
2005; and Di Cesare et al., 2005; reviewed below). All of which have the potential to
become useful in clinical practice in the near future.
Preventive measures for PJI include standard methods to decrease surgical site
infection including systemic antimicrobial prophylaxis. In Europe and in some
centres in the USA the use of antibiotics containing polymethylmethacrylate to fix
the prosthesis as primary prophylaxis is also commonplace and randomized trials
and cohort studies have shown the benefit of this approach. Many implants being
placed now, however, do not require cement for fixation hence the importance of
novel prevention strategies such as using implants with a titanium surface tethered
with vancomycin which have biological activity against infection as a primary
prevention strategy (see Parvizi et al., 2004; reviewed below).
Treatment of PJI is still not well standardized. A generally preferred treatment
strategy is the two-stage revision arthroplasty, which includes removal of the
infected prosthesis and implantation of antibiotic-loaded cement spacer, followed
by prolonged intravenous antibiotics and subsequent re-implantation of a new
prosthesis weeks to months later. The safety of the high-dose antibiotic-
impregnated spacers has been further elucidated recently (see Springer et al., 2004;
© Atlas Medical Publishing Ltd

224 V . I N F E C T I O N C O N T R O L I N PAT I E N T G R O U P S
reviewed below). The usefulness of less invasive techniques that can lower surgical
morbidity (i.e. open irrigation and debridement with hardware retention) has been
explored in recent studies of new treatment algorithms (see Giulieri et al., 2004;
reviewed below). The use of arthroscopic debridement in selected groups of
patients undergoing debridement and retention has the potential to lower the
morbidity of open debridement even more if validated in clinical trials (see Ilahi et
al., 2005; reviewed below).
The limitations of the diagnostic and therapeutic studies in the field of PJI are
related to the lack of well-designed prospective clinical trials, cohort or case–
control studies. Furthermore, any one institution does not see enough patients to
perform trials of adequate sample size, appropriate randomization is often difficult
to obtain or not feasible, and the length of follow-up needed to validate any new
treatment strategy is much longer than for other infectious diseases so studies are
prohibitively expensive.
Future research in the field of PJI should focus on the validation and reliability
of new diagnostic techniques that have been discovered in larger clinical trials as
well as continuing to explore new diagnostic tests. In addition, the results from
well-designed prospective or historical cohort studies to evaluate new medical and
surgical treatment strategies is urgently needed by clinicians caring for patients
with PJI to help guide them to use the best therapeutic modalities for their patients.
Hopefully investigators partnering with industry and the government and other
regulatory approval bodies can find ways to do these studies efficiently. The authors
of the manuscripts in this review should be commended in moving us in this
direction.
✍
Polymerase chain reaction can detect bacterial DNA in
aseptically loose total hip arthroplasties
Clarke MT, Roberts CP, Lee PT, Gray J, Keene GS, Rushton N. Clin Orthop
Relat Res 2004; 427: 132–7
B A C K G R O U N D . The attempt to differentiate between septic and aseptic loosening

in a failed total joint arthroplasty and to define the microbiology of the infection has
always been an important but challenging task. Current diagnostic methods, which
include culture, histological examination, and blood tests (erythrocyte sedimentation
rate [ESR], C-reactive protein [CRP]), have proven helpful. None of these tests,
however, have become the diagnostic test of choice because they lack optimal
sensitivity and specificity.
The use of the PCR technique has been recently evaluated as a means of diagnosing
low-grade bacterial infection in patients with a failed arthroplasty. Most investigators
have tried to detect the 16S ribosomal subunit, which is present in all bacterial
species. The earlier reports from Mariani et al. and Tunney et al. revealed that the use
of PCR provided evidence of low-grade prosthesis infection or colonization in patients
who had had revision arthroplasties that otherwise would have been labelled as
aseptic loosening |3,4|. The first report by Mariani et al. tested 50 patients with a
INFECTIONS IN PROSTHETIC DEVICES 225
symptomatic failed total knee arthroplasty (TKA) |3|. Fifteen instances were both
culture positive and PCR positive, 17 had negative culture and positive PCR, and
18 had both negative culture and negative PCR. The cut-off point used in this study
was 100 bacteria/ml. These investigators suggested that there were no false
positives as there was a negative PCR result in all the negative controls. Six of
18 negative controls, however, produced low-level signal that was below the arbitrary
set point considered positive by the investigators.
Another study by Tunney et al. was able to identify bacterial DNA in 72% of total hip
arthroplasty (THA) revisions after ultrasonic washing of the prosthesis using a cut-off
point at 10 000 bacteria/ml |4|.
This study used a PCR technique to identify bacterial DNA (16S ribosomal subunit)
in patients who underwent revision THA, all of which had negative bacterial culture
and histological study for infection, with the primary THA patients serving as negative
controls. For patients receiving a primary THA, joint aspiration was performed after
skin incision and before joint exposure; three or four specimens were retrieved.
For revision THA, the same procedure was followed with joint aspiration before joint
exposure. Synovium, capsule, and periprosthetic membrane were retrieved as soon as
they were visible. All specimens were sent for both culture and PCR in primary THA
and for culture, histological examination and PCR in revision THA specimens.
I N T E R P R E T A T I O N . This study by Clarke et al. included 28 patients undergoing

31 revision THAs. Bacterial DNA was identified using a cut-off point of 10 bacteria/
1000 μl, which is lower than in previously published studies. Overall, the 31 revision
THA specimens yielded bacterial DNA in 39 (46%) of 85 tissue specimens compared to
18 (21.4%) of 84 specimens (P = 0.001) from patients who had primary THA. Bacterial
DNA was not identified more frequently in the synovial fluid of revision THAs than in that
of primary THA (10.7% vs 9.5%; P = 0.36).
Bacterial DNA was identified in 20 of 105 (19%) of the combined tissue and fluid
specimens from the primary THA patients, which is most probably a result of
contamination during specimen retrieval. Since there are no set criteria for how many
positive PCR samples are needed to diagnose infection, this study was assessed using
three different definitions of infection: (1) infection definition—one or more specimens
was positive by PCR, giving 16/31 (52%)/revision THA vs 8/28 (29%) primary THA
(P = 0.072); (2) infection definition—at least two specimens were positive by PCR, giving
12/31 (39%) revision THA vs 8/28 (29%) primary THA (P = 0.412); and (3) infection
definition—all specimens submitted were positive by PCR, giving 7/31 (23%) revision
THA vs 3/28 (11%) primary THA (P = 0.225).
Comment
This study demonstrates the usefulness of PCR in detecting the presence of
bacterial DNA in patients undergoing revision THA who at the time of surgery had
negative cultures and no histological evidence of infection. This is the first report
suggesting that the use of PCR can create significant false-positive results when
using the cut-off at the lower level of 10 bacteria/ml. The use of primary THA as the
negative control and the high false-positive rates found suggested that the specimen
retrieval process or perhaps, although less likely, the laboratory process, can create a
significant contamination problem. Speciation of the bacteria detected in the

revision arthroplasty specimens to determine whether the bacteria detected were
common environmental contaminants and not typical pathogens may have helped
to distinguish infection or colonization from laboratory contamination. Other
possibilities for these results are that the use of a cut-off level of 10 bacteria/ml,
although the most sensitive level achievable without introducing laboratory-based
false-positive results, may not be biologically reasonable after specimens are
exposed in the operating room, or that a prosthesis can be colonized by bacteria
without causing signs or symptoms of infection using the tests that we use today to
determine the presence of infection.
Using PCR to diagnose low-grade implant infection still requires more data on
what threshold should be used, especially when the number of copies of 16S
ribosomal DNA can vary between bacterial species (typically between four and
seven copies). Bacteria with more 16S are more likely to be detected than those with
fewer copies per cell. Another issue involved is the appropriate specimen to be used
for PCR testing. Whether the specimen should originate from the implant itself
rather than the surrounding tissue is still unknown. PCR will undoubtedly become
an important tool in diagnosing low-grade implant infections because its high
sensitivity enables the detection of a small number of bacteria, but data are still
needed for an appropriate threshold that would be clinically meaningful and would
avoid false positives.
✍
Synovial fluid leukocyte count and differential for the
diagnosis of prosthetic knee infection
Trampuz A, Hanssen AD, Osmon DR, Mandrekar J, Steckelberg JM, Patel R.
Am J Med 2004; 117: 556–62
B A C K G R O U N D . Differentiation between aseptic loosening and prosthetic joint

infection is important. Synovial fluid analysis has traditionally been used to help
diagnose native joint septic arthritis and the criteria for interpretation of synovial fluid
leukocyte count and differential in native joint diseases are established. The criteria
for interpretation of synovial fluid leukocyte count in prosthetic joint infection,
however, are unknown. This study has tried to establish critical values for the synovial
fluid leukocyte count and differential that would allow the clinician to diagnose
prosthetic knee infection.
I N T E R P R E T A T I O N . The synovial fluid leukocyte count and differential appear to be

valuable tools in diagnosing prosthetic knee infection, in particular to differentiate
between aseptic loosening and septic arthritis. When the optimal cut-off values are used
(synovial fluid leukocyte count >1.7 × 103/μl or differential of >65% neutrophils), the
sensitivity and specificity are 94% and 88%, respectively, for synovial fluid leukocyte
count and 97% and 98%, respectively, for the neutrophils differential. These cut-off
values are significantly lower than the ones used to diagnose septic arthritis in native
joints (synovial fluid leukocytes >50 × 103/μl or neutrophils >90%). This could represent
the frequency of low virulence and biofilm phenotype microorganisms causing prosthetic
joint infection.
Comment
This is a prospective study of total 133 synovial fluid specimens in patients who had
undergone synovial fluid aspiration for pre-operative evaluation of arthroplasty
failure that had occurred more than 6 months after arthroplasty implantation.
Patients with underlying inflammatory joint diseases (e.g. rheumatoid arthritis,
psoriatic arthritis), crystal-induced arthropathy, or connective tissue diseases were
excluded. Patients were classified as having either aseptic failure or prosthetic
joint infection based on pre-operative and intra-operative findings. Prosthetic joint
infection was diagnosed if at least one of the following criteria was present: growth
from the same microorganism in at least two cultures of synovial fluid or peri-
prosthetic tissue; visible synovial fluid purulence at the time of arthrocentesis or
during surgery; acute inflammation on histopathological examination; or presence
of a sinus tract communicating with the prosthesis. The synovial fluid leukocyte
count was significantly higher in patients with prosthetic joint infection (median
18.9 × 103/μl; range 0.3 to 178 × 103/μl) than in those with aseptic failure (median
0.3 × 103/μl; range 0.1 to 16 × 103/μl; P <0.0001) Similarly, the percentage of
neutrophils was significantly higher in patients with prosthetic joint infection
(median 92%; range 55–100%) than in those with aseptic failure (median 7%;
range 0–79%; P <0.0001).
The cut-off values for optimal sensitivity and specificity to differentiate aseptic
failure from prosthetic joint infection were 1.7 × 103/μl for synovial fluid leukocyte
count with sensitivity of 94%, specificity of 88%, positive predictive value of 73%
and negative predictive value of 98%. A neutrophil percentage of 65% achieved
sensitivity of 97%, specificity of 98%, positive predictive value of 94% and negative
predictive value of 99%. Previous studies that used higher cut-off values explain the
low sensitivity.
The synovial fluid leukocyte count was also associated with the type of
microorganism in the patients who had not received antimicrobial agents, reflect-
ing differences in microbial virulence; Staphylococcus aureus was associated with
leukocyte counts >100 × 103/μl while coagulase-negative staphylococci were
associated with counts <50 × 103/μl. Propionibacterium acnes and Corynebacterium
jeikeium were associated with leukocyte counts <10 × 103/μl.
In conclusion, synovial fluid examination in prosthetic joint failure has a good
discriminatory ability which would be very important in surgical planning because
the treatment generally required for an infected prosthetic joint often involves
resection arthroplasty followed by delayed implantation instead of revision
arthroplasty during the same procedure.
The limitations of this study include the fact that patients with inflammatory
joint diseases were excluded from the study; patients who developed infection in the
first 6 months following TKA were not included and presumably after implantation
the synovial fluid leukocyte count is elevated for a length of time; and lastly it is
unknown if these results can be generalized to arthroplasties of other joints.
✍
Is ‘aseptic’ loosening of the prosthetic cup after total hip
replacement due to non-culturable bacterial pathogens in
patients with low-grade infection?
Ince A, Rupp J, Frommelt L, Katzer A, Gille J, Lohr JF. Clin Infect Dis 2004;
39: 1599–603
B A C K G R O U N D . Aseptic loosening remains a common complication of THA with

approximately 10% of THAs needing revision after 10 years. Septic loosening of the
prosthesis is the important diagnosis that needs to be excluded before revision
surgery. The standard procedures of Gram stain, culture and tissue biopsy, however,
have been shown to have low sensitivity. There have been several recent reports using
PCR to detect highly conserved regions of the bacterial genomes (16S ribosomal
subunit) in attempts to facilitate the diagnosis of low-grade prosthetic infection. This
study included 24 patients with acetabular cup loosening; only patients without
clinical signs of infection and negative synovial fluid culture were included in the
study. Intra-operative samples were taken from the neocapsule and synovia for routine
culture and PCR detection of 16S ribosomal RNA. Nine patients receiving primary hip
arthroplasty acted as controls.
I N T E R P R E T A T I O N . PCR, routine culture and histopathology results showed no

evidence of prosthetic joint infection in either cases or controls with the exception of one
patient in whom cultures yielded Propionibacterium acnes in routine culturing from a
neocapsular sample. Acetabular tissue, PCR from both sites and histopathological
examination of this patient all gave negative results for any evidence of infection. The
mean CRP and ESR results in the cohort were 5.5 mg/l and 11.96 mm/h, respectively,
whereas the control group results were 4.2 mg/l and 9.56 mm/h. No statistically
significant differences were found. Follow-up examinations of all patients (≥19 months
after revision) revealed no sign of infection and no additional revision was necessary.
Comment
Attempts to use PCR to diagnose low-grade prosthetic infection causing arthro-
plasty failure were initially very encouraging, as suggested by the previous studies of
Mariani et al. and Tunney et al. |3,4|. These studies described increased sensitivity
using the PCR method and reported no false positives in any of the negative
controls. A more recent report by Clarke et al. has reported conflicting data. This
study used sequences of universal primers (16S rRNA gene) that were used in
previous studies and primers for the control gene (GAPDH). However, the
detection threshold in this study was significantly higher than in the previous
studies; although the investigator claimed that bacterial DNA from neocapsule and
acetabular synovia are known to have high levels of background human DNA
and the detection level needed to increase to 10 000 genome equivalents to
Staphylococcus epidermidis/100 μl (or 105 genome/ml) instead of 10 genome

equivalents/100 μl (or 100 genome/ml) from the study by Mariani et al. or 1000
genome equivalents/100 μl (or 104 genome/ml) from Tunney et al.
Therefore, we cannot directly compare these studies and more data and more
development of the techniques are needed to demonstrate if using a lower detection
threshold is technically possible and if that will increase the sensitivity. The recent
study by Clarke et al. illustrates this outcome when using a much lower cut-off
point.
✍
The Mark Coventry Award: white blood cell gene expression:
a new approach toward the study and diagnosis of infection
Deirmengian C, Lonner JH, Booth RE Jr. Clin Orthop Relat Res 2005; 440:
38–44
B A C K G R O U N D . The problem of diagnostic certainty in prosthetic joint infection has

been ongoing; in particular, to differentiate between delayed-onset infection and
aseptic prosthetic loosening. Traditional approaches have included measuring
inflammatory markers, performing imaging studies, joint fluid analysis and culturing
intra-operative periprosthetic tissue for histopathology and culture, all of which have
variable sensitivity and specificity. A newer approach, which has been introduced in
recent years, is the use of PCR to detect bacterial DNA in periprosthetic tissue. The
most recent innovative diagnostic test for PJI to be evaluated is the use of a new
genomic technique to show that synovial fluid white blood cells express a gene
expression ‘signature’ that differentiates septic from aseptic inflammation. The
technique is based on recent knowledge in genomic studies that neutrophils have an
ability to modulate their genomic responses specifically toward differing causes of
inflammation. Neutrophils even have the ability to respond differently toward varying
species of bacteria. The investigators used synovial fluid that was aspirated from
patients with acute S. aureus infections (five samples from infected TKA and two
samples from an infected native knee) or acute gout of the knee. Differential cell
counts included predominantly neutrophils in all aspirates. Riboneucleic acid was
analysed on an Affymetrix U133A GeneChip for detection of gene expression.
I N T E R P R E T A T I O N . The neutrophils from patients who had acute S. aureus septic

arthritis showed a dramatically different gene expression profile when compared to
neutrophils from patients who had acute gout when using the rank products analysis for
the identification of differentially expressed genes. A total of 1615 genes was found to
be differentially expressed (each gene with P <0.05) between the groups and 124 of
these genes associated with P-values between 0.0000001 and 0.0001. The genes in
infection and gout were evenly divided between upregulation and downregulation.
Patients were also regrouped in an effort to find differences in gene expression that may
be attributed to cell count, the presence of arthroplasty, or antibiotic pre-treatment,
which were not found to correlate with differences in gene expression. Among the highly
upregulated genes in infection were multiple interleukins, tumour necrosis factors,
chemokine ligands, and other genes that have previously been shown to be expressed by
in vitro neutrophils activated by microorganisms.
Comment
This pilot genomic diagnostic study shows promising potential in differentiating
the inflammatory response in infectious and non-infectious diseases using neutro-
phils from synovial fluid specimens from native and prosthetic joints. Potential
limitations of the study, as discussed by the investigators, include whether the
difference in gene expression found in this study could represent pre-existing
susceptibility, rather than a responsive change. In addition, because the patients in
this study do not represent patient populations with low-grade prosthetic joint
infection, this population might have different white blood cell gene expression
from patients with S. aureus infection. The investigators argued though that,
theoretically, the gene expression signature in chronic infections should reflect the
same pattern and more data are being obtained to confirm this theory. Lastly, more
studies are needed to confirm this finding with different types of bacteria and in a
larger group of patients with a variety of underlying diseases but undoubtedly, this
technique is potentially very powerful and could become part of the future
diagnostic process in prosthetic joint infection.
✍
Serum interleukin-6 as a marker of periprosthetic infection
following total hip and knee arthroplasty
Di Cesare PE, Chang E, Preston CF, Liu CJ. J Bone Joint Surg Am 2005; 87:
1921–7
B A C K G R O U N D . Difficulties in the diagnosis of PJI have led to efforts in the study of

new diagnostic tests in recent years. It has been accepted that every diagnostic test
in this field has certain limitations in its sensitivity and specificity and no single
radiological or laboratory test can accurately detect infection before revision
arthroplasty. IL-6 is an excellent marker of sepsis |5| and correlates with severity of
sepsis, especially in post-operative patients |6|. IL-6 is produced by monocytes and
macrophages and one of its functions is to stimulate the production of major acute-
phase proteins, including CRP. This study is a prospective, case–control study of
58 patients who underwent revision hip or knee arthroplasty over a 24-month period.
Infection was defined as at least ten polymorphonuclear leukocytes per high-power
field on histological examination of specimens obtained during surgery before
administration of antibiotics and the presence of bacteria on intra-operative cultures.
Seventeen of 58 patients were classified as having infection. Blood samples were
obtained within 24 h of surgery to determine the levels of CRP, IL-6, white blood cell
count and ESR. The mean value of each test result was compared using Wilcoxon
rank-sum (Mann–Whitney) test between patients with and without infection.
I N T E R P R E T A T I O N . The serum IL-6, CRP and ESR were significantly higher in patients
with infection than in those without infection (P <0.05). No significant difference was
found in the white blood cell counts between infected and non-infected patients.
A threshold laboratory value greater than that presumed to be positive for infection was
assigned for the white blood cell count (1.0 × 109), ESR (30 mm/h), CRP level (10 mg/l)
and IL-6 (10 pg/ml), to determine the sensitivity, specificity, negative predictive value,
positive predictive value and accuracy.
The sensitivity and specificity found for IL-6 were 100% and 95%, respectively. These
values for ESR and CRP were 100% and 56%, and 94% and 78%, respectively.
The positive and negative predictive values of IL-6 were reported as 89% and 100%. The
white blood cell count, not unexpectedly, showed a poor sensitivity (47%) but a high
specificity (100%).
Comment
IL-6 has been shown to be an excellent marker of inflammation associated with
infection. A rapid increase with inflammation or major surgery and a rapid return
to normal within 48–72 h after a procedure were shown in a study performed in
joint replacement patients and is a valuable characteristic when trying to distin-
guish elevation caused by surgery from infection |7|. The investigators suggested
that IL-6 could be used alone or in combination with ESR and CRP as one of the
diagnostic tests for periprosthetic infection following THA and TKA and has
potential for use in monitoring response to treatment. Some limitations in using
IL-6 included the non-specific nature of the test because it can be elevated in several
non-infectious situations (i.e. rheumatoid arthritis, multiple sclerosis and major
surgery) |8–10|. HIV infection |11| and acute viral infection have also been shown to
have elevated IL-6.
In addition, because the definition of infection in this study was based in part on
histopathology and because some cases of periprosthetic infection do not have
abnormal histopathology, just positive intra-operative cultures, the utility of IL-6 in
these patient subsets will need to be evaluated. In conclusion, additional pro-
spective studies are needed to confirm the high specificity and sensitivity of IL-6
based on the criteria for infection outlined by the investigators. IL-6 has potential to
become one of the routine diagnostic tests for prosthetic joint infection.
✍
Frank Stinchfield Award. Titanium surface with biologic
activity against infection
Parvizi J, Wickstrom E, Zeiger AR, et al. Clin Orthop Relat Res 2004; 429:
33–8
B A C K G R O U N D . Given the fact that the treatment of periprosthetic infection is

difficult and costly, primary prevention methods are urgently needed. Current primary
prevention strategies, such as the use of systemic antimicrobial prophylaxis, laminar
airflow and antimicrobial impregnated cement, have been used with various reported
success rates. Therefore the need for innovative measures to reduce the risk of
operative contamination of the prosthesis or haematogenous seeding are urgently
warranted |12–14|. The purpose of this study was to design and analyse a ‘smart’ and
self-protecting implant using a method of vancomycin tethering to titanium (Ti)
surface.
I N T E R P R E T A T I O N . Particles of Ti were derivatized with aminopropyl triethoxy silane

(APTS). The Ti-APTS particles were used to charge a solid-phase synthesis column.
Two Fmoc-aminoethoxyethoxyacetic acid linkers, which are spacers for membrane
permeability, were coupled to the Ti-APTS particles followed by automatic coupling of
vancomycin.
Staphylococcus aureus was incubated with Ti-APTS, vancomycin-Ti, or no added metal
for a growth control. At 30 and 60 minutes, aliquots were removed, diluted, and plated
onto bacterial plates. Bacterial colonies were counted after overnight incubation at 37°C
and proliferation was determined as a function of time, treatment, and initial inoculum.
The vancomycin-Ti surface markedly reduced colony numbers at both sampling times
compared with either no added metal or the Ti-APTS.
The bactericidal activity of tethered vancomycin was persistent after repeat incubation
of the vancomycin-Ti with S. aureus on at least three occasions.
Comment
Despite all efforts in the modern era, intra-operative contamination and haemato-
genous seeding of joint prostheses still occur, leading to periprosthetic infection.
Staphylococci account for the majority of periprosthetic infections. To reduce the
risk of prosthesis colonization, investigators have used antibiotic-impregnated
cement. The problems encountered with this strategy are multiple and include the
unpredictability of rate of antibiotic elution, the potential for spacers to become
foreign bodies after the antibiotics have eluted, and the potential to jeopardize
the mechanical properties of the cement and thus fixation of the prosthesis. In
addition, many implants now do not require cement fixation. Other investigators
have attempted to achieve a bioactive implant surface by the use of various coatings
via formation of a thin soft sol-gel, hydrogel or by creation of a surface collagen
matrix. The physical and chemical fragility of the aforementioned coatings have
limited their use. The current authors are proposing a novel approach to covalently
tether vancomycin to a titanium surface. The authors showed an active and
persistent effect in an in vitro model on a S. aureus isolate.
Although promising, this approach warrants further investigation and has several
limitations. For instance the effect on mechanical properties on the titanium would
warrant further investigation. The lack of activity of vancomycin against Gram-
negative organisms is also a potential shortcoming. Furthermore the impact of this
novel method on the rate of periprosthetic infection and the potential impact on
antimicrobial resistance will also need to be studied in prospective clinical trials.
✍
Systemic safety of high-dose antibiotic-loaded cement
spacers after resection of an infected total knee
arthroplasty
Springer BD, Lee GC, Osmon D, Haidukewych GJ, Hanssen AD, Jacofsky DJ.
Clin Orthop Relat Res 2004; 427: 47–51
B A C K G R O U N D . Implantation of antibiotic-impregnated polymethyl methacrylate

cement spacers has been widely used in conjunction with resection arthroplasty,
debridement and prolonged antibiotic therapy followed by delayed re-implantation for
the treatment of prosthetic joint infection. In the USA, most orthopaedic surgeons use
hand-mixed antibiotics into the bone cement to create these spacers; although a Food
and Drug Administration approved PROSTALAC (prosthesis with antibiotics loaded
acrylic cement or spacer) spacer is approved for THA infection |15|. The optimal dose
of antibiotics in these spacers to achieve high local concentrations without systemic
toxicity is unknown. Cohort data on the safety of various dosing regimens remain
scarce. Case reports of renal failure have been published after the use of antibiotic-
impregnated cement. The purpose of this study was to assess the systemic safety of
using relatively high doses of antibiotics in cement spacers.
I N T E R P R E T A T I O N . This is a retrospective study in 34 patients who underwent

resection arthroplasty of an infected TKA followed by implantation of an antibiotic-loaded
cement spacer. The follow-up time was until the time of re-implantation.
All surgeries were performed by A.D.H. The regimens used were 4 g of vancomycin
and 4.8 g of gentamicin per batch of cement. Two to four batches of cement were used
in one spacer, depending on bony deficiency and patient size. Each antibiotic cement
spacer contained an average of 10.5 g of vancomycin (range 3–16 g) and 12.5 g of
gentamicin (range 3.6–19.2 g). All patients were concomitantly treated with 6 weeks of
intravenous antibiotics. Pre-operative creatinine ranged from 0.7 to 1.8 mg/dl with a
mean of 0.9 mg/dl. Seventeen out of 34 patients have risk factors for renal insufficiency
(underlying diabetes, hypertension or both, one patient had a history of interstitial
tubular nephritis and two patients had known chronic renal insufficiency)
The result of this study revealed that only one patient had a transient elevation
of creatinine from 0.7 mg/dl to 1.7 mg/dl on post-operative day 1 which normalized
the next day. No other patients showed any evidence of renal insufficiency or other
systemic side effects of antibiotics during the 6-week course of treatment before
implantation. Three patients (8%) developed recurrence of infection after re-implantation,
two required repeat resection arthroplasty and one underwent resection and
arthrodesis.
Comment
The use of antibiotic-loaded cement spacer after resection of infected arthroplasty
is a common practice. It is believed that this method delivers a high concentration
of antibiotics in a localized area and is safer than systemic administration of
intravenous antibiotics in such doses |16, 17|.
This retrospective study reported no significant adverse effects; in particular,

renal dysfunction or ototoxicity despite using high doses of two potential nephro-
toxic or ototoxic antibiotics in the spacers.
Nevertheless, there is still a need for larger cohort studies looking at different
types of arthroplasty and in different patient populations before final conclusions
can be drawn. It would seem prudent to include in these studies, the use of different
cements with different elution characteristics, different mixing techniques that may
also affect antibiotic elution and to measure serum concentrations of the anti-
biotics when possible.
✍
Management of infection associated with total hip
arthroplasty according to treatment algorithm
Giulieri SG, Graber P, Ochsner PE, Zimmerli W. Infection 2004; 32: 222–8
B A C K G R O U N D . Infection following THA occurs in 1–2% of cases. Management of

THA infection requires multiple surgeries and prolonged use of antimicrobials. This
often necessitates lengthy hospital stays and can result in significant morbidity and
significant healthcare costs. The goal of treatment of a THA infection is the
elimination or control of the infection and restoration of the joint function. There is
significant controversy surrounding the optimal management of patients with THA
infection. Management strategies commonly used to attain that goal are debridement
and component retention, one-stage exchange or two-stage exchange. To date there
are no published randomized clinical trials evaluating these therapeutic modalities.
Management decisions are often based on the level of expertise of the orthopaedic
surgeon, the joint age, symptom duration, the condition of the implant and surrounding
soft tissue and the patient’s overall health status |18–20|. This study evaluates
retrospectively the clinical validity of a preset algorithm at the author’s institution.
I N T E R P R E T A T I O N . Sixty patients with 63 episodes of THA infections from 1985 to

2001 at the Medical University Clinic, Kantonsspital, Switzerland were included in the
study. The treatment algorithm was based on the joint age, symptom duration, condition
of implant and soft tissue and the patients’ overall health status. Three main treatment
options were proposed, debridement with retention or one-stage or two-stage
replacement. Patients with early infection (<3 months after THA) or with acute onset who
had a stable implant and an intact soft tissue envelope were treated with debridement
and component retention. Patients with delayed infection or with subacute or chronic
onset in whom the THA prosthesis was loose but who had either a preserved soft tissue
or slightly damaged envelope were treated with one-stage exchange. Patients with
delayed or late infection (>2 years after arthroplasty) in whom the prosthesis was loose
and had a sinus tract or abscess and who were in good medical condition were treated
with two-stage exchange. The median patient age was 72 years. Patients were followed
for a median of 28 months; 29% were early, 41% delayed, and 30% late infections.
Staphylococcus aureus and coagulase-negative staphylococci were the most commonly
encountered organisms. After the first intervention 83% (52/63) of the episodes had a
favourable outcome. Patients treated according to the proposed algorithm had a better
outcome than if they were not (44/50 = 88% vs 8/13 = 62%; relative risk 0.31; 95%
confidence interval 0.11–0.86, P <0.03).
Comment
Given the lack of published randomized clinical trials to guide the clinician on
the proper management of THA infection, the clinician has to rely on retrospective
data. The decision to retain the prosthesis or to proceed with one- or two-
stage exchange is often complex and is dependent on a set of subjective and
objective parameters. Giulieri et al. have studied the outcome of THA infections
based on a preset treatment algorithm. The outcome was significantly better if the
algorithm was followed. Since all three surgical modalities had a similar outcome if
the algorithm was followed, the authors are proposing that a two-stage exchange
surgery not be favoured over one-stage exchange or debridement and retention if
the preset criteria for each of these modalities are met and their medical treatment
strategies are followed. Given the inability to analyse other confounding factors
because of the retrospective nature of this study, it would be reasonable to validate
the proposed algorithm in a large multicentre prospective study.
✍
Arthroscopic debridement of acute periprosthetic septic
arthritis of the knee
Ilahi OA, Al-Habbal GA, Bocell JR, Tullos HS, Huo MH. Arthroscopy 2005; 21:
303–6
B A C K G R O U N D . The standard treatment for PJI in the USA is a two-stage exchange

procedure that has a reported success rate >90%. This method of treatment is time
consuming and involves two major surgeries, a prolonged immobilization period which
compromises function and the possibility of new complications, i.e. extensor
mechanism dysfunction.
Another option of treating prosthetic joint infection is open debridement, irrigation
and retention of components, which in a previous study by Mont et al. |21| report a
success rate of 100% in immediate post-TKA infection (ten knees) and 71% (ten out of
14) in late haematogenous prosthetic knee infections. All patients presented within
30 days of symptoms appearing. A newer surgical approach for debridement and
retention of a knee prosthesis using arthroscopic debridement has been proposed with
the potential to decrease surgical morbidity by avoiding a large arthrotomy and
allowing early mobilization. Earlier reports, however, have shown conflicting data.
Successful outcomes were published in a few case reports, which were performed
early in the course of infection. Several other reports have shown unfavourable
outcomes.
This study involved all patients who presented with an infected knee arthroplasty
under the care of a single surgeon (HST) between August 1998 and July 1999.
All patients were screened for suitability for treatment with an arthroscopic
debridement protocol. The screening criteria included (1) a stable, well-functioning
prosthesis pre-infection, (2) symptoms for less than 1 week, and (3) no immune
system compromising factors. Exclusion criteria included radiographic signs of

loosening, symptoms for more than 1 week or patients immunocompromised as a
result of medications such as corticosteroids or chronic disease such as diabetes
mellitus or rheumatoid arthritis. Patients who met the inclusion criteria underwent
arthroscopic debridement through inferomedial, inferolateral and superomedial portals
with the superolateral portal added as needed, along with major synovectomy and
irrigation with minimum of 12 litres of antibiotic solution, 6 weeks of intravenous
antibiotics, suction drains for 48 h or until drainage was less than 20 ml/8 h and
repeat arthroscopic debridement if fever persisted beyond 48 h. Patients were
followed for at least 36 months after debridement.
I N T E R P R E T A T I O N . During the study period, there were five knees in four patients that
met the inclusion criteria and that were treated per protocol. Mean follow-up time was
41 months (range 36–43 months) and no patients were lost to follow-up. The mean time
of debridement was 3.8 days from the onset of symptoms (range 3–5 days) and no
patient required more than one debridement. There were no polymicrobial infections,
three knees were infected with Streptococcus pneumoniae, one knee was infected with
coagulase-negative staphylococcus, and one with Streptococcus intermedius.
All patients received 6 weeks of intravenous antibiotics followed by 2–4 weeks of oral
antibiotics as determined by the infectious diseases consultant. During the study period,
none of the patients underwent revision because of infection. One knee underwent
polyethylene exchange because of wear at 18 months without evidence of infection
at the time of operation. No patients required long-term oral suppressive antibiotics.
The result from this study supported the use of arthroscopic debridement and
hardware retention in the setting of acute PJI in a selected group of patients with
symptom onset of <7 days, no radiographic evidence of loosening and no
immunosuppressive condition.
Comment
Treatment of infected prosthetic joint using open irrigation, debridement and
retention of component is the alternative method to control PJI in selected patients
|21|. Arthroscopic debridement, which is less invasive than open arthroscopy, can
provide the patients with less surgical morbidity and enhanced early mobilization.
Previous studies in this topic have shown conflicting results. The large prospective
study by Waldman et al. |22| showed a 38% success rate using arthroscopic irriga-
tion and debridement (six out of 16) which was performed in a selected group of
patients who had a symptom duration of <7 days without radiographic evidence of
loosening; ten patients required hardware removal within 7 weeks and two cases
required arthrodesis for persistent infection.
Dixon et al. |23| reported a retrospective case series of 15 patients who underwent
arthroscopic debridement for infected total knee replacement with 60% success
rate but the inclusion and exclusion criteria for using this method of treatment
were not mentioned.
In contrast to previously described studies, this small study by Ilahi et al. suggests
that the use of rigid criteria in selecting patients with infected knee arthroplasties
for arthroscopic debridement can result in an excellent outcome. The surgical

technique used for arthroscopy in this study is three portals and an additional
portal if needed to access synovitis, which is different from Waldman et al. who only
used two portals of entry; the use of extensive arthroscopic synovectomy with at
least 12 litres of antibiotic irrigant and post-operative suctioning until drainage was
less than 20 ml/8 h are also different from previously mentioned studies.
The major weakness of this well-designed study is the lack of statistical power
caused by the small number of patients. We are still in need of a large comparative
study using strict inclusion and exclusion criteria with the proposed surgical
techniques of arthroscopy and other treatment modalities (suctioning and
antibiotic treatment) before arthroscopy for this indication can become common
practice.
✍
The value of hip aspiration versus tissue biopsy in
diagnosing infection before exchange hip arthroplasty
surgery
Williams JL, Norman P, Stockley I. J Arthroplasty 2004; 19: 582–6
B A C K G R O U N D . An attempt to diagnose PJI before revision arthroplasty is an

important aspect of treating a failed prosthesis. The diagnosis of infection
pre-operatively can be facilitated by clinical signs and symptoms, radiographic studies
and inflammatory markers as well as by joint aspiration. Pre-operative hip aspiration
has also been used widely. The investigators proposed obtaining tissue biopsy for
additional culture. It was hypothesized that the technique of tissue (drill) biopsy would
improve the accuracy of simple aspiration because a sample of joint capsule would
give a more accurate diagnosis. In this study, the investigator compared the results of
aspiration versus tissue drill biopsy against three tissue specimens obtained during
open surgery through retrospective study.
Tissue specimens at revision arthroplasty were taken from a minimum of three
sites: capsule, behind the acetabular component and from femoral shaft and used as
definitive microbiological specimens in assessing the presence of infection.
I N T E R P R E T A T I O N . Pre-operative joint aspiration and tissue drill biopsies were

performed in 338 consecutive arthroplasties 3–6 months before definite surgery.
Three hundred and eleven patients subsequently received revision arthroplasty and
27 cases did not proceed to surgery. Complete data were available for 273 patients
(273 hips). Seventy-one out of 273 hips were found to be infected as confirmed by
definitive operative specimens. Growth from one specimen usually was regarded as a
contaminant after discussion with a consultant microbiologist. The most common
causative organisms were coagulase-negative staphylococci (60%), Enterococcus sp.
(7%), and S. aureus (6%). In the confirmed infected hip arthroplasty group (71 cases),
there were 14 aspiration specimens and 12 tissue drill specimens that were sterile. In
the confirmed cases of aseptic loosening, 13 aspirations and 21 tissue drills were not
sterile. These data resulted in 80% sensitivity and 94% specificity in hip aspiration
specimens and 83% sensitivity and 90% specificity in pre-operative tissue biopsy
specimens.
Comment
The result of this study argued against using tissue drill biopsy to augment the
diagnosis of infected hip arthroplasty compared to standard hip aspiration
cultures. It was proposed by the investigator that using the technique of tissue
(drill) biopsy by obtaining a sample of joint capsule would give a more accurate
diagnosis but the results from this study show comparable sensitivity and specificity
from a simple hip aspiration. There are no other data in the literature regarding the
use of this technique for diagnosis of prosthetic joint infection. Given the invasive
nature of this procedure, which needs to be done under general anaesthesia, and no
added benefit, the conclusion from current knowledge should discourage
physicians from using this procedure as a diagnostic tool.
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(N) Infection 06, Ch13 18/7/06 12:57 Page 223

© Atlas Medical Publishing Ltd

B A C K G R O U N D . The attempt to differentiate between septic and aseptic loosening

INFECTIONS IN PROSTHETIC DEVICES 225

I N T E R P R E T A T I O N . This study by Clarke et al. included 28 patients undergoing

significant contamination problem. Speciation of the bacteria detected in the

B A C K G R O U N D . Differentiation between aseptic loosening and prosthetic joint

I N T E R P R E T A T I O N . The synovial fluid leukocyte count and differential appear to be

INFECTIONS IN PROSTHETIC DEVICES 227

B A C K G R O U N D . Aseptic loosening remains a common complication of THA with

I N T E R P R E T A T I O N . PCR, routine culture and histopathology results showed no

INFECTIONS IN PROSTHETIC DEVICES 229

Staphylococcus epidermidis/100 μl (or 105 genome/ml) instead of 10 genome

B A C K G R O U N D . The problem of diagnostic certainty in prosthetic joint infection has

I N T E R P R E T A T I O N . The neutrophils from patients who had acute S. aureus septic

B A C K G R O U N D . Difficulties in the diagnosis of PJI have led to efforts in the study of

INFECTIONS IN PROSTHETIC DEVICES 231

B A C K G R O U N D . Given the fact that the treatment of periprosthetic infection is

I N T E R P R E T A T I O N . Particles of Ti were derivatized with aminopropyl triethoxy silane

INFECTIONS IN PROSTHETIC DEVICES 233

B A C K G R O U N D . Implantation of antibiotic-impregnated polymethyl methacrylate

I N T E R P R E T A T I O N . This is a retrospective study in 34 patients who underwent

This retrospective study reported no significant adverse effects; in particular,

B A C K G R O U N D . Infection following THA occurs in 1–2% of cases. Management of

I N T E R P R E T A T I O N . Sixty patients with 63 episodes of THA infections from 1985 to

INFECTIONS IN PROSTHETIC DEVICES 235

B A C K G R O U N D . The standard treatment for PJI in the USA is a two-stage exchange

system compromising factors. Exclusion criteria included radiographic signs of

INFECTIONS IN PROSTHETIC DEVICES 237

for arthroscopic debridement can result in an excellent outcome. The surgical

B A C K G R O U N D . An attempt to diagnose PJI before revision arthroplasty is an

I N T E R P R E T A T I O N . Pre-operative joint aspiration and tissue drill biopsies were

INFECTIONS IN PROSTHETIC DEVICES 239

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