Sử dụng kháng sinh pps

Journal of the American Academy of Orthopaedic Surgeons
38
In 1970, Buchholz and Engelbrecht
1
introduced the concept of impreg-
nating acrylic bone cement with
antibiotic as a possible means of
preventing infection in patients
undergoing total joint arthroplasty.
Since then, antibiotic-impregnated
cement has become more commonly
used for revision total joint arthro-
plasty and, as antibiotic-impregnated
cement spacers or beads, for treat-
ment of infection during two-stage
revision arthroplasty than it has for
infection prophylaxis in primary
total joint arthroplasty. Even with-
out the contribution of antibiotic-
impregnated cement, the infection
rate after standard primary total
joint arthroplasty in modern oper-
ating rooms has been reduced to
between 0.3% and 2%. A survey
from 1995 concerning orthopaedic
operating room practices and equip-
ment suggested that this reduction
has been achieved by the access to
laminar airflow (present in 49% of
hospital operating rooms), body
exhaust suits (in 69%), high airflow

(in 85%), and ultraviolet lights (in
14%).
2
Reported infection rates after
revision total joint arthroplasty vary
widely because of the large number
of patient variables.
Several types of acrylic bone
cement in current use incorporate
antibiotics, either premixed by the
manufacturer or added by the sur-
geon in the operating room. In the
United States, commonly used
cements such as Palacos (Smith &
Nephew, Memphis, TN), Simplex
(Howmedica, Rutherford, NJ),
CMW (DePuy, Warsaw, IN), and
Zimmer (Zimmer, Warsaw, IN) are
mixed with antibiotics by the sur-
geon. Commercially prepared ad-
mixtures such as AKZ (Simplex P
with colistin and erythromycin),
Refobacin-Palacos R (Palacos R with
gentamicin cement), and Septopal
(beads of Palacos R with genta-
micin) are not currently available in
the United States. Some hospital
pharmacies (2.2%) prepackage ce-
ment with antibiotic for later use in
the operating room.

3
A survey of 1,015 orthopaedic
surgeons in the continental United
States revealed that 56% have im-
pregnated their bone cement with
antibiotic for at least some cases.
2
Surgeons specializing in joint recon-
struction were more likely to use
antibiotic in bone cement (88%).
Sixty-five percent of all surgeons
surveyed reported that they adjust-
ed antibiotic usage according to
microbial sensitivity; of this group,
70% used tobramycin; 26%, genta-
micin; 18%, vancomycin; 15%,
cephalosporins; and 3%, combined
antibiotics. Antibiotics in liquid
Dr. Joseph is resident, Department of Ortho-
paedic Surgery, Musculoskeletal Research
Center, NYU–Hospital for Joint Diseases, New
York, NY. Dr. Chen is resident, Department of
Orthopaedic Surgery, Musculoskeletal Research
Center, NYU–Hospital for Joint Diseases, New
York. Dr. Di Cesare is Associate Professor of
Orthopaedic Surgery, Department of Ortho-
paedic Surgery, Musculoskeletal Research
Center, NYU–Hospital for Joint Diseases, New
York.
Reprint requests: Dr. Di Cesare, 15th Floor,

301 East 17th Street, New York, NY 10003.
Copyright 2003 by the American Academy of
Orthopaedic Surgeons.
Abstract
The use of antibiotic-impregnated cement in revision of total hip arthroplasty pro-
cedures is widespread, and a substantial body of evidence demonstrates its effi-
cacy in infection prevention and treatment. However, it is not clear that
it is necessary or desirable as a routine means of prophylaxis in primary total
joint arthroplasty. In the management of infected implant sites, antibiotic-
impregnated cement used in one-stage exchange arthroplasties has lowered rein-
fection rates. In two-stage procedures, use of beads and either articulating or
nonarticulating antibiotic-impregnated cement spacers also has lowered reinfec-
tion rates. In addition, spacers reduce “dead space,” help stabilize the limb, and
facilitate reimplantation. Problems associated with antibiotic-impregnated
cement in total joint arthroplasty include weakening of the cement and the genera-
tion of antibiotic-resistant bacteria in infected implant sites.
J Am Acad Orthop Surg 2003;11:38-47
Use of Antibiotic-Impregnated Cement
in Total Joint Arthroplasty
Thomas N. Joseph, MD, Andrew L. Chen, MD, and Paul E. Di Cesare, MD
Thomas N. Joseph, MD, et al
Vol 11, No 1, January/February 2003
39
form, generally considered to be
less desirable than the powdered
form (because of the effects to
cement polymerization), were used
by as many as 11% of the surgeons
surveyed, possibly because of the
general unavailability of a pow-

dered form of gentamicin in the
United States. In performing prima-
ry arthroplasties, approximately
12% of surgeons always used anti-
biotic-impregnated cement, 69%
never used it, and 19% used it some-
times. Of those who did use it, 68%
did so in less than one third of their
aseptic revision total joint arthro-
plasties. However, over 80% used it
more than two thirds of the time in
septic revision total joint arthroplas-
ty. Over half often used antibiotic-
impregnated cement beads in two-
stage reimplantation for infections;
32% often used antibiotic-impreg-
nated cement spacers in hips; and
69% often used such spacers in
knees. Of those using antibiotic-
impregnated cement, 28% used a
single-stage reimplantation in total
joint arthroplasty infection, while
72% used a two-stage approach.
2
These data suggest that no com-
monly accepted standard exists
regarding the use of antibiotic-
impregnated cement in orthopaedic
surgery.
The FDA takes no official posi-

tion on the use of antibiotics in
cement. A document issued July 17,
2002, requires that cement labeling
contain the warning, “PMMA bone
cement is contraindicated in the
presence of active or incompletely
treated infection, at the site where
the bone cement is to be applied.”
4
Laboratory Studies
A number of criteria must be met
for antibiotics to be effective when
mixed with methylmethacrylate.
The preparation must be sufficiently
thermally stable to withstand the
heat of polymerization. The antibi-
otic must not be adversely affected
by body temperature and must be
water soluble so that it can diffuse
into surrounding tissues. The
antibiotic must have a bactericidal
effect at the tissue levels attained;
furthermore, it must be released
gradually over an appropriate time
period. The preparation must
evoke minimal local inflammatory
or allergic reaction. Development of
resistance should be rare to nonexis-
tent; common pathogens must be
considered, including Staphylococcus

aureus, S epidermidis, coliform, and
others, such as anaerobes. Finally,
the antibiotic must not significantly
compromise mechanical integrity,
especially if the cement is used for
implant fixation.
In vitro analyses of antibiotic elu-
tion and mechanical stability have
been done with a variety of antibiot-
ic-cement combinations. The stable
incorporation of aminoglycoside
antibiotics (eg, gentamicin and
tobramycin) into cement and their
elution therefrom are well estab-
lished. Vancomycin is gaining pop-
ularity because of its effectiveness
against methicillin-resistant bacteria
as well as its general availability.
Although penicillins and cephalo-
sporins exhibit adequate elution and
stability, they are often avoided be-
cause of their potential allergenicity.
In one study, in vitro testing of van-
comycin- and tobramycin-impreg-
nated cement demonstrated elution
of antibiotic for the entire 9-week
study period; the highest elution
rate occurred at 18 hours (between 3
and 5 times the rate that occurred at
72 hours).

5
Ciprofloxacin, a more re-
cent addition to bone cement, may
gain in popularity because of its
wide antibiotic spectrum and gener-
al availability. Ciprofloxacin elution
met or exceeded the minimum
inhibitory concentration for com-
mon organisms associated with
osteomyelitis for up to 42 days.
6
Recent studies
7,8
indicate that
ciprofloxacin may inhibit bone, liga-
ment, and soft-tissue healing; this is
a concern, particularly in total knee
revision surgery.
Lipids may impede the leaching
process from cement. The peptide
antibiotics vancomycin and poly-
myxin B nonapeptide have been
shown to elute for a longer period
than do the nonpeptide antibiotics
gentamicin, novobiocin, and eryth-
romycin.
9
Molecular weight also
appears to play a role. One in vitro
study indicated that vancomycin is

eluted 10 times less efficiently than
tobramycin from antibiotic-impreg-
nated cement, probably because of
its higher molecular weight.
10
Other
in vitro studies, however, found no
marked difference between the two.
11
Palacos cement appears to pro-
vide the best elution profile for most
antibiotics. A study of the elution
characteristics of Palacos and CMW
acrylic cements showed that CMW 1
released 24% less tobramycin and
36% less vancomycin than did Pala-
cos; CMW 3 released 34% less tobra-
mycin and 38% less vancomycin.
5
Another in vitro study, in which
Palacos and Simplex beads and
spacers were impregnated with 4 g
of either vancomycin or tobramycin
in 40 g of cement, also showed
antibiotic eluting from Palacos at
higher levels.
12
Concentrations re-
mained above the minimum inhibi-
tory concentration for S aureus

longer in Palacos than in Simplex.
In another study, elution of van-
comycin, daptomycin, and amikacin
from Palacos exceeded that of
Simplex, Zimmer Dough-Type, and
Zimmer LVC.
13
Commercially prepared antibiot-
ic cement may be superior to intra-
operatively mixed cement. Elution
of gentamicin and tobramycin from
laboratory-customized Zimmer,
Simplex, or Palacos beads compared
with elution from commercially pre-
pared gentamicin-PMMA (Septopal)
beads showed that more total an-
tibiotic was eluted from the latter,
and was maintained at higher con-
Antibiotic-Impregnated Cement in Total Joint Arthroplasty
Journal of the American Academy of Orthopaedic Surgeons
40
centrations, than it was in the beads
to which antibiotics were added by
the investigators.
14
The results of studies of the effect
on elution of combinations of antibi-
otics, typically vancomycin and
tobramycin, are inconclusive. In one
study, elution of vancomycin was

minimally affected by tobramycin,
while elution of tobramycin was
reduced by vancomycin.
10
In anoth-
er study, the elution rate of tobramy-
cin increased by 68% and that of van-
comycin by 103% when these antibi-
otics were combined.
15
In the first
study,
10
vacuum-mixed Simplex was
used, and in the second,
15
nonvacu-
um-mixed Palacos. In both, the most
advanced means of measuring an-
tibiotic were used. An in vivo study
using the prosthesis of antibiotic-
loaded acrylic cement (PROSTA-
LAC; Smith & Nephew, Memphis,
TN) demonstrated a statistically sig-
nificant (P = 0.011) increase in the
elution of vancomycin when the
dose of tobramycin was increased
from 2.4 to 3.6 g per dose of cement;
Simplex was used in 12 patients and
Palacos in 37.

16
The investigators
changed the cement early in their
study after finding evidence in the
literature suggesting better antibiotic
elution from Palacos.
Klekamp et al
10
demonstrated that
compressive and fatigue strength
decreased with the addition of van-
comycin or tobramycin to cement.
Cement impregnated with 1, 2, or 3
g of vancomycin failed at 90%, 70%,
and 50%, respectively, of the num-
ber of cycles to failure for antibiotic-
free cement. Likewise, cement with
1.2 and 2.4 g of tobramycin failed at
80% and 60%, respectively, of the
number of cycles to failure for con-
trols. Although fatigue strength
data were statistically significant (P
< 0.05), the results of compressive
strength tests demonstrated a de-
creasing trend yet were not statisti-
cally significant. Routinely used
lyophilized vancomycin was found
to greatly reduce cement fatigue
strength. The authors suggested
using vancomycin P (an ultrafine

powder) in bone cement intended
for prosthesis fixation because it has
less detrimental effect on cement
strength. Askew et al
17
found that
the addition of 1 g of either tobra-
mycin or vancomycin resulted in
nominal bending strength reduc-
tions (6% and 1%, respectively,
compared with controls). Another
study confirmed that the addition of
1.2 g of tobramycin to 40 g of Sim-
plex powder did not significantly de-
crease fatigue strength.
18
Vancomy-
cin L (lyophilized) should be finely
ground when used for prosthesis
fixation to prevent mechanical
weakening; however, large crystals
should not be completely pulver-
ized when preparing beads or spac-
ers because the crystals facilitate
antibiotic elution.
Morita and Aritomi
19
showed no
reduction in tension and bending
strengths of cefuzonam-impregnated

cement when <3 g was used. Earlier
studies showed similar results with
respect to compressive and tension
strengths of cement impregnated
with gentamicin, oxacillin, and cefa-
zolin.
20
Addition of more than 4.5 g
of gentamicin has been shown to
substantially weaken cement to a
level below that appropriate for
implant fixation.
21
Reduction of no
more than 10% in bone cement
strength is considered acceptable for
use in total joint arthroplasty fixa-
tion; however, weaker antibiotic-
impregnated cement may be used in
beads and spacers. Table 1 lists ap-
propriate doses of antibiotic im-
pregnation in cement for prosthesis
fixation and for spacers and beads.
Vacuum mixing, which reduces
the number of voids in bone ce-
ment, improves the mechanical
properties of antibiotic-impregnated
cement. When cylindrical cement-
vancomycin specimens were sub-
jected to fatigue testing (uniaxial

mode), cycles to failure were 15% to
58% greater in vacuum-mixed speci-
mens than in those mixed at atmos-
pheric pressure. Fracture of antibi-
otic-impregnated cement specimens
during cyclic testing was reduced
up to tenfold with vacuum mixing
or with vigorous pulverizing of the
antibiotic before mixing.
10
Another
study showed vacuum mixing also
reduced fivefold the radiograph-
ically apparent porosity of antibiotic-
impregnated cement specimens but
may inhibit antibiotic release.
17
In
Table 1
Reported Doses
*
of Antibiotics Used in Antibiotic-Impregnated
Cement
13,26,44,53-55
Antibiotic Dose for Prosthesis Fixation Dose for Spacers and Beads
Amikacin 1 g 2 g
Cefazolin NR 4 to 8 g
Cefotaxime 3 g NR
Cefuroxime 1.5 to 3 g NR
Clindamycin NR 4 to 8 g

Erythromycin 0.5 to 1 g NR
Gentamicin 1 g 2 to 5 g
Ticarcillin Not appropriate 5 to 13 g
Tobramycin 1.2 g 2.4 to 9.6 g
Vancomycin 1 g (vancomycin P) 3 to 9 g (vancomycin P or L)
*
Per 40-g batch of cement
P = ultrafine powder, L = lyophilized, NR = not reported in the literature
Thomas N. Joseph, MD, et al
Vol 11, No 1, January/February 2003
41
one study, vancomycin vacuum-
mixed with Simplex (1:40 ratio)
released slightly less than half the
antibiotic that air-mixed cement did;
no antibiotic release was detectable
after 48 hours.
13
Another study,
however, found adequate antibacte-
rial activity lasting for 21 days.
17
Dextran has been used to en-
hance porosity and thus improve the
elution of antibiotic. One prepara-
tion with dextran released approxi-
mately 4 times as much antibiotic as
did a dextran-free preparation, and
elution remained detectable for 10
days versus 7 days, respectively.

13
However, dextran degrades the
mechanical properties of cement;
therefore, its use for prosthetic fixa-
tion should be extremely limited.
Centrifugation, another preparation
technique, markedly increased the
fatigue life of Simplex both with and
without tobramycin by a factor of
eight.
Increase in the surface area of
antibiotic-impregnated cement spac-
ers has been shown to increase elu-
tion of antibiotic in vitro. Holtom et
al
22
demonstrated that fenestrated
spacers with a 40% greater surface
area resulted in a 20% higher elution
rate of vancomycin from Palacos ce-
ment than from standard or donut-
shaped spacers. Masri et al
23
demon-
strated a significant (P = 0.05) in-
crease in the elution of tobramycin
over 1 week with the use of Simplex-
impregnated blocks that had a 9%
increased surface area-to-volume
ratio.

Antibiotics in liquid form mixed
with cement dilute the catalyst that
is needed for the cement curing
process, thereby adversely affecting
both the curing time and final
mechanical properties of cement;
accordingly, they are not recom-
mended. Table 2 lists antibiotics
that can be mixed with cement.
In Vivo Studies
The penetration of antibiotics re-
leased from antibiotic-impregnated
cement into surrounding tissues has
been evaluated in both animal and
human studies. Concentrations of
antibiotic in hematoma, granulation
tissue, and bone vary according to
antibiotic. Local concentrations,
however, have been found to be
consistently higher than serum con-
centrations and usually exceed the
minimum inhibitory concentrations
for target pathogens.
The elution of several antibiotics
from Simplex cement was measured
in samples from dogs over a 28-day
period.
24
Clindamycin, vancomy-
cin, and tobramycin exhibited elu-

tion characteristics that reached con-
sistently high levels in bone and
granulation tissue. Cefazolin and
ciprofloxacin were maintained at
high concentrations in granulation
tissue but at low levels in seroma
and bone. Ticarcillin showed unfa-
vorable elution characteristics in
granulation tissue, seroma, and
bone.
Experimentally produced para-
spinal wounds (fractured, infected
spinous processes) in rabbits were
treated with either a chain of to-
bramycin antibiotic-impregnated
cement beads, beads without antibi-
otics, systemic antibiotics only, or
nothing.
25
At 5 days, no recoverable
organisms were found in six of eight
animals treated with antibiotic-
impregnated cement beads. Six of
eight rabbits receiving systemic
tobramycin had wound infections.
All five animals in which nonantibi-
otic-impregnated cement beads were
implanted had significant infections;
one died from sepsis. All four ani-
mals that received no treatment were

infected.
Antibiotic concentrations were
measured in wound drainage fluid,
urine, and serum from 50 patients
who underwent primary total hip
arthroplasty (THA) and received
tobramycin or vancomycin deliv-
ered either in antibiotic-impregnated
cement or by intravenous adminis-
tration (not both).
26
No significant
differences were found between
Table 2
Antibiotics Used in Antibiotic-Impregnated Cement
Decreased
Activity Because Adversely Affected
Can Be Mixed With Cement of Cement Heat by Cement Curing
Amikacin Cefuzonam Erythromycin Penicillin Chloramphenicol Liquid gentamicin,
Amoxicillin Cephalothin Gentamicin Polymyxin B Colistimethate clindamycin, etc (because
Ampicillin Ciprofloxacin (powder) Streptomycin Tetracycline of aqueous content)
Bacitracin Clindamycin Lincomycin Ticarcillin Rifampin
Cefamandole (powder) Methicillin Tobramycin
Cefazolin Colistin Novobiocin Vancomycin
Cefuroxime Daptomycin Oxacillin
Antibiotic-Impregnated Cement in Total Joint Arthroplasty
Journal of the American Academy of Orthopaedic Surgeons
42
Simplex and Palacos surgeon-
prepared antibiotic-impregnated

cement. Serum and urine antibiotic
levels were significantly (P ≤ 0.05)
higher in the intravenous group
than in the impregnated-cement
group. Wound drainage fluid levels
of tobramycin were significantly (P
≤ 0.05) higher in the antibiotic-
impregnated cement group than in
the intravenous group, whereas the
vancomycin intravenous group had
higher antibiotic levels in wound
drainage fluid than did the van-
comycin cement group. In the
cement group, tobramycin exhibited
a consistently high level of bioactivity
against S epidermidis in wound
drainage fluid, while vancomycin
lost all bioactivity by 24 hours. In
30% of cases, no vancomycin was
detected in the wound drainage
fluid of the cement group. Overall,
tobramycin exhibited adequate local
tissue levels and released antibiotic
effectively, whereas vancomycin
exhibited inadequate elution prop-
erties.
Clinical Studies
Primary Total Joint
Arthroplasty
Because of the low rates of infec-

tion experienced with total joint
arthroplasty procedures, researchers
seeking to demonstrate statistically
significant differences with the pro-
phylactic use of antibiotic-impreg-
nated cement require a very large
sample size with multicenter partici-
pation. A prospective, randomized
study in Sweden combined results
from nine orthopaedics departments
(1,688 consecutive THAs) to com-
pare the prophylactic effect of
systemic antibiotics to that of genta-
micin-impregnated cement alone.
At a mean follow-up of 10 years, the
infection rate was 1.6% in the sys-
temic antibiotic group and 1.1% in
the gentamicin-impregnated cement
group, a difference that was not sta-
tistically significant.
11
No cases of
nephrotoxicity, ototoxicity, or aller-
gic reaction were reported.
More than 10,000 primary ce-
mented total hip replacements done
for osteoarthritis and reported to the
Norwegian arthroplasty registry
were studied retrospectively.
27

Four
groups were compared: patients
receiving antibiotic prophylaxis both
systemically and locally in antibiotic-
impregnated cement, those receiv-
ing antibiotics only systemically,
those receiving only antibiotic-
impregnated cement, and those
receiving no antibiotic prophylaxis.
The antibiotic-impregnated cement
was either Palacos with gentamicin
or AKZ (erythromycin and colistin
with Simplex). The rate of revision
done for any reason was 2.0%
(94/4,586) in patients receiving only
systemic antibiotics, 4.2% (10/239)
for antibiotic-impregnated cement
only, 1.2% (70/5,804) for the com-
bined regimen, and 2.5% (7/276) for
no antibiotics. Among cases that sub-
sequently required revision for in-
fection, the lowest revision rate,
0.14% (8/5,804), was in patients who
received both antibiotic-impregnated
cement and systemic antibiotics.
A prospective, randomized clini-
cal trial of 401 patients in two
British centers compared the effect
of cefuroxime-impregnated cement
and cefuroxime administered sys-

temically on infection after total
joint arthroplasty.
28
No statistically
significant difference was found
between the two groups with
respect to incidence of superficial
wound infection or early deep infec-
tion (1% in both groups). There
were no late deep infections after 2-
year follow-up.
Hope et al
29
found at least one
strain of gentamicin-resistant coag-
ulase-negative staphylococcus in 30
of 34 cases of deep infection (88%) in
which cement containing gentamicin
had been used. In contrast, only 9
of 57 patients (16%) in whom antibi-
otic-free cement was used exhibited
gentamicin-resistant coagulase-neg-
ative staphylococcus.
Revision Arthroplasty
Revision arthroplasty usually is
accompanied by rates of infection
significantly higher than rates for
primary arthroplasty. Revision
arthroplasties done for infection are
either one- or two-stage procedures.

Two-stage revisions are more com-
mon, but they can be technically
demanding because of scar forma-
tion, limb shortening, disuse osteo-
porosis, and altered anatomy.
Although advocates of two-stage
reimplantation cite infection rates
lower than those of one-stage revi-
sions, carefully selected patients can
be treated with comparable success
with one-stage revisions using
antibiotic-impregnated cement. In
one review of the literature, success
rates of one-stage exchange with and
without the use of antibiotic-impreg-
nated cement were 81% and 71%,
respectively; the success rates of
two-stage reimplantation with and
without antibiotic-impregnated
cement were 93% and 82%.
30
One-Stage Revision for Infection
One-stage exchange arthroplasty
using antibiotic-impregnated ce-
ment has been advocated in defined
instances for the treatment of an
infected total joint arthroplasty. In a
multicenter comparison of one- and
two-stage exchange arthroplasties
for infection conducted in the 1970s,

a success rate of approximately 80%
was found for both methods.
31
Gentamicin-loaded Palacos and 6
months of systemic antibiotics were
used in all procedures. The results
were slightly better for one-stage
exchanges; however, follow-up was
relatively short (0.5 to 3.5 years). In
a study of 235 one-stage exchanges
for THA infection using antibiotic-
impregnated cement, 11% with per-
sistent infection failed; another 3% of
cases with suspected infection
failed.
32
Of the 61 two-stage ex-
changes, which used antibiotic-
Thomas N. Joseph, MD, et al
Vol 11, No 1, January/February 2003
43
impregnated cement beads for peri-
ods of from 6 weeks to 9 months, 5%
failed from reinfection. Hope et al
29
reviewed a series of 91 patients with
deep infection of a cemented
THA caused by coagulase-negative
staphylococcus. In this series, 72 pa-
tients were treated with one-stage

exchange arthroplasty; 9 (13%)
failed because of recurrence of infec-
tion. Gentamicin was used in com-
bination with other antibiotics based
on organism sensitivities. The other
19 patients underwent a two-stage
exchange without any failures.
Although it has been suggested
that a contraindication to one-stage
reimplantation is infection with a
gram-negative organism, a study of
15 patients with gram-negative
infection treated with one-stage
THA revision found only 1 recur-
rence (6.7%) at a mean follow-up of
8 years. Palacos cement with gen-
tamicin was used in 13 of 15 pa-
tients, with other antibiotics added
to cement as appropriate.
33
In a
larger study of 183 patients with
similar follow-up (mean, 7.75 years),
one-stage revision with both antibi-
otic-impregnated cement and sys-
temic antibiotics was used for deep
infection of a THA.
34
Twenty-nine
of these patients (16%) had evidence

of persistent infection and 154 (84%)
were free of infection on follow-up.
None of the 29 patients who experi-
enced failure was infected with
gram-negative organisms.
For patients undergoing revision
arthroplasty, Garvin et al
35
devel-
oped a classification system of
high-risk, suspicious, and definite
infection categories. These were
based on Gram stains, cultures,
intraoperative findings, clinical diag-
noses, radiographic findings, and
laboratory results.
35
In a prospec-
tive clinical study, gentamicin-
impregnated Palacos was used for
prosthesis fixation in 67 high-risk,
32 suspicious, and 31 definite infec-
tions. All but one of the high-risk
patients underwent one-stage pro-
cedures; those with suspicious or
definite infections underwent either
one- or two-stage procedures plus 6
weeks of intravenous antibiotics.
Postoperative infection occurred in
5 of the 92 one-stage patients (5.4%)

and in none of the 38 two-stage
patients. Of the 67 high-risk
patients, 3 (4.5%) developed post-
operative infections; one was then
revised with a successful two-stage
procedure. Of the 32 patients suspi-
cious for infection, 19 underwent
one-stage implantation; one of them
developed a postoperative infection.
The other 13 patients with suspi-
cious infection underwent success-
ful two-stage implantation. Of
patients with definite infection, 7 of
31 underwent one-stage implanta-
tion, with one of them developing a
postoperative infection; 24 patients
had a successful two-stage implan-
tation.
To test that one-stage revisions
can be successful if rigid criteria are
met, Ure et al
36
prospectively fol-
lowed 20 consecutive patients under-
going one-stage THA for infection
between 1979 and 1990. Surgical
management included meticulous
débridement, use of antibiotic-
impregnated cement, and systemic
antibiotic therapy. Patients were

excluded from this treatment when
they were immunocompromised,
had an infection with a known resis-
tant gram-negative or methicillin-
resistant organism, or had a major
skin, soft-tissue, or osseous defect.
At a mean follow-up of 9.9 years, no
patient had experienced recurrence
of infection. Two patients required
revision for aseptic loosening.
Parenteral antibiotics were adminis-
tered postoperatively for a mean of
4.7 months.
Two-Stage Revision for Infection
By reducing dead space, cement
spacers help stabilize the limb
awaiting reimplantation (Fig. 1).
Complications include bone loss,
dislocation, continued pain, de-
creased mobility, and (rarely) frac-
ture. Local antibiotic delivery with
cement spacers, cement beads, or a
PROSTALAC has been used after
component removal in a two-stage
procedure. Additionally, antibiotic-
impregnated cement can be used for
prosthesis fixation during reimplan-
tation in the second stage.
Antibiotic-impregnated cement
spacers used in the first stage of

two-stage reimplantation can deliv-
er a high concentration of antibiotics
to the infected area. In a retrospec-
tive study, Calton et al
37
treated 25
infected total knee prostheses in 24
patients with débridement, compo-
nent removal, and insertion of an
antibiotic-impregnated cement block.
Intravenous antibiotics were admin-
istered for 6 weeks; patients’ knees
were kept immobilized with no
weight bearing. The success rate
was 92% (2 failures) at a mean fol-
low-up of 36 months; 15 of 25 knees
exhibited either tibial or femoral
bone loss caused by invagination of
the cement spacer block into the
cancellous bone. Leunig et al
38
re-
ported on 12 patients with deep
infections of hip implants who un-
derwent two-stage revision and
were treated using gentamicin-
loaded cement. Spacers were used
for a mean of 4 months; during that
period, six spacers failed, five by
dislocation and one by fracture. At

a mean follow-up of 27 months after
reimplantation arthroplasty, all
patients were mobile and infection
free.
An articulating spacer used in
two-stage revision for infected total
knee arthroplasty may improve
patient mobility and allow partial
weight bearing. This would pro-
mote healthier soft tissues, improve
wound healing, allow easier reim-
plantation, improve bone quality
and range of motion, and reduce
complications. Hofmann et al
39
treated 26 patients who had late-
infected total knee arthroplasties
with two-stage revision using an
articulating spacer with tobramycin-
Antibiotic-Impregnated Cement in Total Joint Arthroplasty
Journal of the American Academy of Orthopaedic Surgeons
44
impregnated cement. The spacer
was prepared by cleaning, autoclav-
ing, and reinserting the femoral
component. A new tibial polyethyl-
ene insert and in some cases a new
all-polyethylene patellar component
were used to place a large amount
of antibiotic-impregnated cement

between each insert and bone.
Patients were treated with 6 weeks
of intravenous antibiotic therapy.
Reimplantation was performed 6 to
12 weeks after placement of the
spacer. All but one patient (who
died of systemic complications)
underwent successful reimplanta-
tion (96%). At a mean follow-up
of 31 months, knee scores had
improved and no recurrence of in-
fection was found.
Complications of early articulat-
ing spacers included tibiofemoral
instability and patellar instability;
results subsequently have improved
with design modifications. A recent
study by Fehring et al
40
failed to
show any difference in range of
motion or knee scores between
articulating and static antibiotic-
impregnated cement spacers used
in two-stage revisions. The ar-
ticulating spacers were custom-pre-
pared using a stainless steel femoral
component mold and stemmed tibial
baseplate of antibiotic-impregnated
cement. Nevertheless, reimplanta-

tion was facilitated, and less bone
loss occurred with articulating spac-
ers than with static antibiotic-
impregnated spacers.
Lai et al
41
reported on 40 infect-
ed hip prostheses treated with
component removal, intravenous
and oral antibiotics for 8 weeks,
and delayed reimplantation (mean,
48 weeks) with cementless compo-
nents. At mean of 4 years’ follow-
up, 5 patients (13%) had experi-
enced recurrent infection: 2 of 33
from the group treated with Sep-
topal (gentamicin) beads, and 3 of 6
of those treated without antibiotic-
impregnated cement beads. A pro-
spective, randomized, multicenter
study of 6 infected total knee and 22
infected hip arthroplasties in 28
patients compared two-stage re-
implantation using gentamicin-
impregnated cement beads with
that using conventional parenteral
systemic antibiotic therapy for 6
weeks postoperatively.
42
At a mean

follow-up of 3 years, infection
recurred in 2 of 15 patients treated
with gentamicin-impregnated
cement beads (13%) and in 4 of 13
patients treated with conventional
systemic antibiotic therapy (31%);
however, this was not statistically
significant. Whiteside
43
used allo-
graft technique with cementless
revision arthroplasty for massive
tibial and femoral defects in 33
chronically infected total knee
arthroplasties. Treatment included
implant removal, débridement, and
rigidly fixed antibiotic-soaked bone
graft followed by 6 weeks of antibi-
otic-impregnated cement beads and
intravenous antibiotics. The success
rate of the two-stage procedure was
85%. Infection recurred in five knees;
however, repeated procedures al-
lowed successful revision in all but
one, which required an above-the-
knee amputation. Although use of
antibiotic-impregnated cement beads
or spacers is common in two-stage
revisions, one study showed that
their use in two-stage revisions was

not correlated with cure rate for
infection.
44
The PROSTALAC, introduced in
1989, is a temporary hip prosthesis
composed of a thin polyethylene
acetabular cup and a stainless steel
femoral component, both of which
are loosely cemented with antibiotic-
impregnated cement (Fig. 2). Bene-
fits include early mobilization, accel-
erated rehabilitation, and early hos-
pital discharge. The device maintains
soft-tissue planes and leg lengths
and has made second-stage proce-
dures easier to perform. Younger et
al
45
reviewed 48 patients who had
Figure 1 Anteroposterior (A) and lateral (B) radiographs of an antibiotic-impregnated
cement spacer in a two-stage revision total knee arthroplasty.
A B
Thomas N. Joseph, MD, et al
Vol 11, No 1, January/February 2003
45
undergone two-stage arthroplasty of
an infected hip replacement using
the PROSTALAC. All but three pa-
tients were free from persistent
infection, for an eradication rate of

94%. More recently, Younger et al
46
evaluated PROSTALACs with a
cement-on-cement articulation and
with a custom metal-on-polyethyl-
ene articulation. Of 28 infected total
hips followed for a minimum of 2
years, 96% exhibited no evidence of
infection.
In a retrospective study of 89 re-
vision procedures for infected total
knee arthroplasties, persistent infec-
tion occurred in 10 knees (11.2%).
44
No standardized protocol was used
for treatment. In 64 knees, antibiotic-
impregnated cement was used for
implant fixation; in 25, no antibiotic-
impregnated cement was used.
Antibiotic-impregnated beads were
used in 20 patients, antibiotic-
impregnated spacers in 23, both
used in 4, and neither used in 42
patients. When use of antibiotic-
impregnated cement for implant fix-
ation was factored in, the results
were statistically significant. Of the
25 knees without antibiotic-impreg-
nated cement, 7 (28%) developed
recurrent infection, compared with

only 3 (5%) of the 64 knees treated
with antibiotic-impregnated cement
(P < 0.01). Although antibiotic-
impregnated cement beads or spac-
ers appeared to be beneficial, their
use was not statistically significant.
We are not aware of any prospec-
tive randomized study comparing
antibiotic-impregnated cement
beads or spacers to antibiotic-
impregnated cement in prosthetic
fixation.
Antibiotics in Revision Arthroplasty
Without Infection
Although the use of antibiotic-
impregnated cement in revision
arthroplasty without evidence of
infection has been advocated, the
literature on the subject is scant and
equivocal. Lynch et al
47
reported
notably better results with genta-
micin-containing cement for aseptic
revisions than with cement alone
(systemic antibiotics not used), a
reduction from 3.5% to 0.8%. A ret-
rospective analysis with minimum
2-year follow-up reported that in
aseptic revision THAs or conversion

from upper femoral prosthesis (pro-
phylactic systemic antibiotics not
used), infection rates were 0.5% for
gentamicin-impregnated cement
and 2.8% for cement alone.
47
The
authors concluded that low-viru-
lence organisms that are difficult to
culture may be present in some
cases thought to be aseptic loosen-
ing and that the local antibacterial
effect is responsible for the effective
prevention and treatment of infec-
tion in these patients.
Experimental Cement-Antibiotic
Combinations
Ceramic composites have been
considered for use as a vehicle for
antibiotic delivery. In one laboratory
study of a novel bioactive bone ce-
ment (15% bisphenol-α-glycidyl
methacrylate, 15% triethylene-glycol
dimethacrylate resin, and 70%
apatite- and wollastonite-containing
glass-ceramic powder) containing
cephalexin in the form of pellets,
antibiotic release was initially rapid,
slowed markedly after 24 hours, and
was released continuously thereafter

for 2 weeks.
48
The strength of the
cement with cephalexin was approxi-
mately twice that of acrylic antibiotic-
impregnated cement. The authors
suggested that this material may be
suitable for prosthetic fixation as
well as in beads or spacers. Another
study tested the efficacy of a calcium
hydroxyapatite ceramic with gen-
tamicin in the form of blocks im-
planted adjacent to stainless steel
tibial inserts in rats that had been in-
jected with S aureus.
49
Suppression
of infection in the ceramic-genta-
micin–treated animals was superior
to that in controls, including those in
which acrylic antibiotic-impregnat-
ed cement was used.
Biodegradable antibiotic-impreg-
nated material offers a potential
means of local antibiotic delivery for
infection control or treatment with-
out obligation for later removal. A
biodegradable cement (composed of
tricalcium phosphate and calcium
carbonate with a matrix phase of

polypropylene fumarate cross-
linked with methylmethacrylate
monomer) containing gentamicin
and vancomycin was evaluated for
treatment and prophylaxis of S
aureus osteomyelitis in rat proximal
tibias.
50
The treatment group exhib-
ited significantly (P < 0.01) fewer
colony-forming units than did con-
trols. Sites treated prophylactically
developed no infections. No signifi-
cant difference was found between
biodegradable cement and PMMA
used as a carrier for antibiotics.
Another study showed that the ten-
sile strength of the material and the
biologic activity of the antibiotic
were maintained when gentamicin
was added to a resorbable calcium
phosphate cement composed of
β-tricalcium phosphate, monocal-
Figure 2 Anteroposterior radiograph of
the PROSTALAC in a two-stage revision
THA.
Antibiotic-Impregnated Cement in Total Joint Arthroplasty
Journal of the American Academy of Orthopaedic Surgeons
46
cium phosphate monohydrate, and

water.
51
More recently, calcium hydrox-
ide has been added to PMMA beads
containing tobramycin.
52
The beads
released hydroxyl and calcium ions
into the culture medium as well as a
greater amount of antibiotic than
did beads containing only tobramy-
cin. Bacterial growth was more
effectively inhibited when S aureus
was incubated with tobramycin-
and calcium hydroxide–impregnat-
ed PMMA disks than with disks
containing only tobramycin. The
study did not, however, address the
effects of the tobramycin and calci-
um hydroxide combination on the
strength of the cement. Future uses
may include fracture healing and
bone grafting in addition to osteo-
myelitis treatment and implant
attachment.
Summary
Since its introduction in 1970, antibi-
otic-impregnated cement has been
used in total joint arthroplasty in a
variety of situations. In both one-

and two-stage revision procedures
for infection, antibiotic-impregnated
cement clearly reduces the reinfec-
tion rate. The antibiotic should
be chosen based on the infecting
organism or, if preoperative cul-
tures are unavailable, by assessment
of likely pathogens. In two-stage
procedures, the use of articulating
spacers implanted with antibiotic-
impregnated cement may improve
reimplantation results as well as
quality of life in the period between
procedures. There is some sugges-
tive evidence that if cement is to be
used in apparently aseptic revision
surgery cases, the cement should be
antibiotic-impregnated because of
the possibility that these culture-
negative cases are indeed contami-
nated. Because of the low rate of
infections with established periop-
erative and intraoperative protocols
and the risk that using antibiotics
will lead to the development of
antibiotic-resistant bacteria, the rou-
tine use of antibiotic-impregnated
cement appears to be unnecessary
in primary total joint replacement
surgery. The future of antibiotic-

impregnated cements may include
stronger composites with more sus-
tained release of a wide array of an-
tibiotics. Bioabsorbable antibiotic-
impregnated cements may further
reduce reinfection rates in one-stage
procedures by supplying additional
local delivery of antibiotic via mate-
rials that do not require later re-
moval.
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