Download Periprosthetic joint infections

Periprosthetic joint infections
Petri Virolainen1, Mikko Manninen2,3
Department of Orthopedics and Traumatology, University Hospital of Turku
Department of Joint Replacement Surgery, Kymenlaakso Hospital, Kotka
3
Eira Hospital, Helsinki
1
2
Infection is a dramatic complication of total joint surgery. Infection mechanism, pathogen, clinical presentation, and patient related factors dictate
the treatment and they should be used as guides to optimal treatment
protocol. The prompt diagnosis and treatment of infection will minimize
the morbidity. No single test is able to show the presence of infection in
every case. Diagnosis of infection is always a combination of available
tests and clinical knowledge.
If acute infections are treated without delays the prosthesis may be saved.
In chronic infections the two stage treatment protocol is still the best
choice. However, especially with elderly patients with many comorbidities, suppression treatment with antibiotic only must be kept in mind.
Mechanism of infection
Infections can be divided into four main categories:
Acute intraoperative infections, delayed postoperative
infections, acute hematogenous infections and chronic infections, table 1.
Acute intraoperative infections are contaminations
and they can be further divided into immediate and
early infections. This was formerly the most common
mechanism of infection. In some series the widespread use of profylactic antibiotics and laminar airflow
conditions have altered especially the rate of intraoperative infections (1) but this is a bit controversial (2).
It seems that the rate of acute postoperative infections
has been quite constant during the last decade. In acute infection the onset of symptoms is very rapid. These infections are relatively easy to diagnose. The early acute infection usually shows characteristic clinical
(pain, warmth and effusion of the joint) and laboratory features (elevated C-reactive protein and blood
leucocyte level).
Delayed postoperative infection is also a contamination. Diagnosis of delayed postoperative infection is
more problematic. The joints are commonly the ones
142 SOT 2•2009
that have not ”healed properly”. Patients are not happy with the outcome, tenderness, impaired function
and pain still exist after several months after surgery.
During the first postoperative months the distinction
between delayed postoperative infection and normal
postoperative pain and dysfunction is clinically very
demanding, sometimes impossible. Laboratory tests
are not helpful. C-reactive protein and blood leucocyte levels are often elevated in delayed infections, but
occasionally also in non-infected cases. Radiographs
show infections very late if ever and bone scans usually show normal postoperative changes also in infected
cases.
Hematogenous infections are not surgery related.
The primary focus of infection is most often in pulmonary or urinary track or in dental area. Skin problems and poor nutrition are also common findings.
Hematogenous infection can act as an acute infection
with classical characteristic clinical and laboratory features. The joint has been asymptomatic and the onset of symptoms is rapid. Hematogenous infection is
often a septic disease with classical septic clinical and
laboratory features.
Suomen Ortopedia ja Traumatologia Vol. 32
Table 1. Classification of periprosthetic joint infections. Acute intraoperative infections can be divided into the immediate and early infections, and late chronic infections can further divided into the late chronic and late chronic
”acutized” infections. These categories help to determine the treatment.
Immediate
Early
0-3 weeks 3wk-3months
Local
symptoms
Swelling
Pus
Pain
Redness
Heat
Systemic
symptoms
CRP
Fewer
Sepsis possible
High
X-ray
Normal
Swelling
Slow rehabilitation
Warmness
Pus discharge
None
Normal or
elevated
Normal
Delayed
3-24 months
Swelling
Slow rehabilitation
Warmness
Pain
None
Normal
or slightly
elevated
RLL’s possible
The diagnosis of chronic infection depends on the
duration of symptoms. These infections can further
be divided into late chronic and late chronic activated infections. The acute phase constitutes the first six
weeks, following subacute phase, after which the infection is called chronic.
The chronic infection is the most difficult to diagnose. Chronic infection can be a contamination or a
hematogenuos infection from origin. Distinction between aseptic loosening and infection is important for
prediction of the final outcome after revision arhtroplasty but also for the choice of surgical management.
In chronic infections laboratory and radiological findings are often normal. Chronic infection is usually
clinically silent, but it may activate and act as an acute infection with classical symptoms. It is, however,
important for the choice of the treatment to distinct
the chronic infections from the true acute hematogenous infection. In true acute infection the joint has
been functioning well before rapid onset of symptoms
whereas in “acutized” chronic infection there has been
some kind of problems (at least minor) with the joint
also earlier.
The most usual bacterial source in postoperative
contamination infections is staphylococcus aureus.
Staphylococcus epidermidis is also quite common. In
chronic infections staphyloccus epidermidis and aureus are the most common pathogen but streptococcus
(5–10%), anaerobic pathogen (5%) and multibacterial
Suomen Ortopedia ja Traumatologia Vol. 32
Acute
hematogenous
Swelling
Pain
Redness
Heat
Fewer
Sepsis possible
High
Normal
Late chronic
>24 months
Late chronic
"acutized"
None or
Bad joint bemild swelling comes even
and /or warm- worse
ness
Pain
None
May be fewer
May be
elevated
May be
elevated
RLL’s possible
RLL’s possible
infections are not uncommon. Acute hematogenous
infections are caused most often by gram-positive cocci, staphylococcus aureus, beta-hemalytic streptococci, entococcus specian, but rarely by a gram negative
pathogen (3–6).
The prosthesis acts as a large foreign body and it
can be colonized by micro-organisms. Experimental
studies have shown that especially polymethylmetacrylate (bone cement), stainless steel, cobalt-chromium
alloy and polyethylene, that are the main constituents
of prostheses, all have increased suspectility to infection (7,8). Especially stafylococcus epidermidis has a
high rate of adhesion to polyethylene. Bacterial resistance to antibiotics is related to the production of a
glococalyx slime that impairs antibiotic access and killing by host-defence mechanisms (9,10).
Risk factors of infection
The best way to prevent an infection is to minimize all
risk factors. However, patients who need prosthesis are
usually elderly and have also other diseases. Rheumatoid patients may have medications that impair bone
formation. Arthroplasty is always a compromise between existing risk factors and hope for better function. Prior surgery of the joint is a significant risk factor.
The risk is significantly higher if surgery is undertaken within one month of the prior arthroplasty. This
is sometimes necessary in revision arthroplasties. Ex2•2009 SOT 143
ceeding operation time is an other risk factor. Studies
have shown that if the operation lasts more than 2.5
hours the risk for infection rises significantly. However, the patient related factors are the most important
factors. Comorbidities, such as diabetes mellitus and
rheumatoid arthritis, increase the risk of infection, as
does poor nutrition and obesity. Immunosupressive
therapy and compromised immune status also increase the risk of infection,. Compromised social factors, mental retardation, smoking and use of alcohol
have been shown to be related to higher infection rate.
Poor hygiene and use of narcotics should be considered as contraindications for arthroplastic surgery.
Diagnosis of infection
As mentioned previously the early acute infection usually shows some characteristic clinical and laboratory features, whereas the diagnosis of subacute or low
grade chronic infection is more problematic. In septic postoperative infections wound drainage is considerable and even pus may be found. C-reactive protein and blood leucocyte level are clearly elevated. In
acute hematogenous infection the wound may seem
normal, but patients have clear tenderness and pain
in motion. Clinical series, however, have shown that
it is not possible to differentiate between the delayed
or chronic infection or aseptic loosening by clinical
signs (6). Pain, especially pain at rest, is more often
related to chronic infections, but also associated with
aseptic loosening. Swelling, tenderness and warmth of
the joint area are also seen in both cases. The blood
white cell count is significantly higher in patients with
infection compared to aseptic loosening. The average
value can, however, still be within normal range. The
blood white cell count is therefore rarely abnormal in
chronic infections and is not helpful for ruling out infections. The blood C-reactive protein level is more
helpful. CRP level is significantly higher in infections
compared to aseptic loosenings, but normal C-reactive protein level does not rule out chronic infection.
It must also be determined whether any other factors
associated with raised C-reactive protein level, such as
rheumatoid arthritis, other infection, any inflammatory condition or neoplasm, is present.
Radiographs are widely used in follow-ups. However, distinction between aseptic loosening and infection is difficult. Clinical follow-up series have showed that radiological findings such as loosening and
osteolysis are common on both septic and aseptic fai144 SOT 2•2009
lures. A common radiological scaling of loose vs. not
loose is not diagnostic. Bone scans are found to very
helpful but problems exists with them too. The sensitivity of Technetium-99m bone scan is in most series
around 0.4 and the specificity 0.95 (6,11). The analysis seems to be very specific but negative bone scan
does not necessarily rule out infection. The scan might
be occasionally negative in patients who have infection but have an inadequate blood supply of the bone
(11). Also, normal postoperative changes are difficult
to differentiate from low grade infection.
Intraoperative frozen section gram staining (12,13)
and aspiration biopsies (14,15) have been found insensitive to detect occult septic loosening. However,
the use of histological grading system based on the
number and the type of the inflammatory cells suggested by Mirra et al. (16) has showed significantly better results (17,18).
Duff et al. (19) reported in their analysis of 43
knees preoperatively aspirated that the preoperative aspiration of the knee was the most helpful study for diagnosis or exclusion of infection with 100%
sensitivity and specificity. Erythrocyte sedimentation
rate, peripheral leukocyte count and radiographs correlated poorly with infection (19). The best results are
obtained from pre- and perioperative joint aspirations
and tissue sample cultures (6,19). An additional benefit of joint aspiration is the possibility to identify
the organism responsible for infection and its antibiotic-sensitivity profile. However, a special attention must be addressed to prevent contamination. PCR
from joint aspiration has been used lately in exceeding
numbers. It is relatively sensitive and specific. PCR,
however, is not able to show antibiotic-sensitivity profile. It is clear from various studies that no single test
is able to show the presence of infection in every case.
Synovial fluid leucocyte differential of >65 % neutrophils and / or leucocyte count over 1700 / µl (20) or
over 1100 / µl (21) are sensitive and spesific tests for a
periprosthetic joint infection at least in knee joint.
Classical clinical signs, laboratory tests, special
imaging studies and joint aspirations have all yielded a
notable rate of false negative results.
Management of infection
Management of infection is a combination of surgical
treatment and antibiotic therapy. Selection of surgical
treatment dictates the antibiotic regimen. The goal of
the treatment should be final eradication of the patSuomen Ortopedia ja Traumatologia Vol. 32
hogen with optimal functional recovery. However, patient related factors may lead to a compromise where
prosthesis retention with long term antibiotic suppression therapy may be the treatment of choice.
Antibiotic therapy is essential to the treatment
of infected prosthesis. Although antibiotics have
been used in various ways for years the exact dosage,
time and route of administration are still open issues
(2,22,23).
In general , high-dose prolonged intravenous antibiotic therapy is recommended for at least six weeks
in cases where implant is removed. Retention of implant results in longer antibiotics regimen. The pathogen and infection mechanism dictates the antibiotic
used. Positive intraoperative cultures are caused predominantly by coagulase negative staphylococci which
are often resistance to beta-lactam antibiotics. However, the resistance varies from one hospital to another.
Staphylococcus aureus, the most dominant pathogen
in acute infections is treated most effectively with and
antistaphylococcal penicillin or first/third-generation
cephalosporin. In areas where methicillin resistant stapylococcus aureus (MRSA) is a major problem vancomycin remains the first line therapy for MRSA infections (24). Possible alternatives for MRSA infections
include trimethoprim-sulfamethoxazole, quinolones
and cubicin. Coagulase-negative staphylococci as a
group (mainly Staphylococcus epidermidis) is the most
common pathogen in late and chronic infections. Antistaphylococcal penicillin and cephalosporin could
be used. Rifampisin has been shown to potentiate the
effect of cephalosprin and should be accompanied to
antibiotic regimen. However, rifampisin has serious side effects and should be used carefully. Coagulase negative staphylococci are more commonly resistant to antibiotics than staphylococcus aureus. Studies
have shown that even in cases where clinical specimens
are reported to be sensitive to beta-lactam antibiotics,
it is possible that resistant organisms are present at the
site of the infection. The use of vancomycin in the treatment of coagulase negative staphylococci is therefore
generally widely recommended (25-28).
Entorococci are more resistant than other common cocci to many antibiotics, especially to cephalosporins. The most common enterococci in prosthesis
infections, entorococcus faecalis is usually susceptible
to penicillins and carpapens but not to nafcillin, or
oxacillin. It is often resistant to quinupristin and dalfopritin. Entorococcus faecium is less common. It is
often resistant to all penicillins and carpapenems and
Suomen Ortopedia ja Traumatologia Vol. 32
vancosin, but sensitive to quinupristin/dalfopristin
and linezolid.
Gram negative bacilli, which are seen in small
number in both acute and chronic infections are especially sensitive to quinolones, but third-generation
cephalosporins and carpapens (especially meropenem)
have also usually good activity (28–30). Prosthetic infections are difficult to treat because of earlier mentioned production of glycocalyx slime. Antibiotic penetration is not optimal. Therefore combination therapy
with two or three different sensitive antibiotics is commonly recommended. Duration of antibiotic therapy
is also a matter of continuous discussion. I.v. administration is recommended for at least 6 to 8 weeks.
However, some antibiotics for example quinolones
can be administered orally from the beginning.
In some cases suppression antibiotic treatment
without any surgical methods may be the best solution for the patient, especially for elderly people with
comorbidities. The risk for reinfection with antibiotic
treatment only is about 30%.
Surgical management of infection
The type of infection dictates the treatment protocol.
Debridement with retention of the prosthesis seems to
be potentially successful treatment for early postoperative infection or acute hematogenous infection, if performed within the first two-three weeks after the onset
of symptoms (31) It is an attractive treatment option
because of lesser morbidity and reduction in cost. The
results have, however, been quite variable (22,32,33).
In acute postoperative infections within three weeks
of operation the prosthesis could be saved. As mentioned these patients have septic symptoms. Intra-articular synevectomy, debridement of all infected tissue with lavage can be recommended within the first
three weeks, however, the results decline by time significantly. Radiological evidence of osteolysis is associated with high rate of failure (1). In delayed postoperative infections the distinction between normal
postoperative pain and loss of function and infection
is difficult. The symptoms are less dramatic. If infection is suspected more than four weeks after operation
prosthesis can usually not be salvaged. If symptoms
are not severe the status could be followed and if infection still suspected after several weeks the joint aspiration shoud be undertaken. In case of infection two
stage exchange is recommended.
Acute hematogenous infection can happen anyti2•2009 SOT 145
me. The onset of symptoms is rapid, patient had not
have any signs of pain or tenderness in the joint previously. The original infection focus should be located. Acute hematogenous infections can be treated
with synovectomy, debridement of all infected tissue,
lavage, replacement of all polyethylene inserts and retention of the prosthesis if not loose. Antibiotic therapy for six weeks is accompanied to treatment protocol
(1–3). The source of the original infection has to be
removed.
In failed arthroplasties the distinction between
aseptic loosening and chronic infection is important
for the choice of surgical management between direct
one stage exchange or delayed two-stage reconstruction. The one-stage exchange means that implant removal and new implantation are done in the same operation. In two stage exchange the implant is removed,
intracapsular synovectomy and power lavage is undertaken. The joint space is filled with antibiotic-cement
spacer. I.v antibiotics are administered for at least six
weeks and after that a new operation is performed.
Synovectomy and power lavage is repeated and new
prosthesis is implanted. The one-stage exchange of infected prosthesis is associated with higher rate of reinfections, and should therefore only be used in the treatment of aseptic loosening or with patients having
chronic infection with low grade pathogen and poor
general medical condition. However, there is some
evidence that the overall results in infected cases can
be improved by careful selection of patients (34). Delayed two-stage reconstruction with the use of antibiotic-impregnated bone cement provides the highest
rate of success in treatment of infection and the best
long-term functional results (1,23,32,33,35–37). Antibiotic bone cement seems to protect against hematogenous infection for some months after operation.
The results of resection arthroplasties are quite
good in terms of eradication, but the procedure is seldom used due to impaired function. It does not seem
to decrease the risk of death. Resection arthroplasty
should be reserved for patients whose medical condition is poor and who have a history of failed prosthesis
sparing surgery.
Infection remains to be one of the most dramatic
complications of joint arthroplastic surgery. The risk
for infection remains the rest of the life. The most effective way to treat infection is to avoid them. Therefore, selection of patients, minimizing the risk factors and using skillful and experienced operative team
can not be underestimated. The financial outcome of
146 SOT 2•2009
infection is significant. Long morbidity and hospital
stay, expensive antibiotic regimen, and repeated operative treatment is a real challenge for the patient and
for the health care system. In future the rate of infections might even decrease but the total number of infection is going to exceed due to the increasing number of arthroplastic operations worldwide. Although,
the goal of treatment has to be the eradication of the
pathogen, modern effective management of patients
with prosthesis infection should not be directed only
toward the eradication of the infection but also toward
the restoration of the optimal function.
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