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Prosthetic joint infections. A role for prophylaxis

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A Role for Prophylaxis
Total joint replacement has been clearly established as one of the major therapeutic advances in
rheumatology (1). It is estimated that as many as
200,000 total joint arthroplasties were performed during 1988 in the US alone (2). The joint prostheses most
frequently implanted are the hip and the knee (3). A
successful operation may enable a patient to continue
or to resume daily work and leisure-related activities;
however, an unsuccessful operation may result in
significant morbidity, with functional impairment and
even death (3,4).
Infection remains the most serious and the most
dreaded complication with a prosthetic joint; infection
is responsible for a significant proportion of the cases
of prosthetic loosening and failure (2-8). Improvements in surgical techniques and prosthetic design, the
perioperative use of antibiotics, and the recognition of
the high-risk patient (2-12) have contributed significantly to the reduction in the occurrence of early
prosthetic joint infections. Late prosthetic joint infections, their cause, and their prevention continue to be
a subject of much discussion among internists, primary care physicians, orthopedic surgeons, rheumatologists, and dentists (13-32). Although general and
specific guidelines for the prophylactic use of antibiFrom the Department of Medicine, Division of Clinical
Immunology and Rheumatology, The University of Alabama at
Birmingham, and the Birmingham Veterans Administration Medical
Center, Birmingham, Alabama.
Warren D. Blackburn, Jr., MD: Associate Professor of
Medicine; Graciela S. Alarcbn, MD, MPH, Professor of Medicine.
Address reprint requests to Graciela S . A l a r c h , MD,
MPH, 603 MEB, UAB Station, The University of Alabama at
Birmingham, Birmingham, AL 35294.
Submitted for publication April 12, 1990; accepted in revised form June 15. 1990.
Arthritis and Rheumatism, Vol. 34, No. 1 (January 1991)
otics in the prevention of late prosthetic joint infection
have been proposed (33), such a regimen is far from
being accepted as the standard of care. The lack of
data to prove the benefit of the prophylactic use of
antibiotics in preventing prosthetic joint infection, the
cost, the potential risk, and the possible legal implications of accepting such recommendations as the “standard of care” have been cited as reasons not to accept
the general prophylactic use of antibiotics.
We review here the available literature on the
subject, present data on the practice patterns of antibiotic prophylaxis for patients with prosthetic joints
among health care professionals in the state of Alabama, and give some general recommendations to the
practicing clinician, based on the data gathered from
the literature and that generated at our institution.
Review of the literature
Early prosthetic joint infection. Soon after prosthetic joint replacement began to be performed, it
became apparent that early infections were a major
problem. Fortunately, infection of the prosthesis during insertion has been greatly reduced during recent
years. Initial studies from the 1960s, evaluating total
hip replacements, reported infection rates approaching
10% (34,35). Patients with early prosthetic joint infection typically will have persistent joint pain. Fever,
drainage, and swelling are present in the minority of
A number of studies have demonstrated that the
patient’s skin, the airborne bacteria in the operating
room, bacteria shed from operating room personnel,
and contaminated instruments and fluids can be
sources of these early prosthetic joint infections (35-
37). Prolonged duration of surgery, increased numbers
of persons in the operating room, and inexperience of
the primary surgeon have been associated with higher
rates of infection at the time of initial prosthetic joint
placement (1 1,38). Previous surgery or prior infection
in the joint appear to increase the likelihood of infection of the prosthetic joint. Patients with rheumatoid
arthritis (RA) appear to be at higher risk of early
prosthetic joint infection than are patients with osteoarthritis. Older patients and patients taking immunomodulatory medications also are at higher risk
(1 1,38). Preliminary studies are inconclusive as to
whether RA patients who are maintained on methotrexate through surgery have a higher rate of postoperative complications (39,40).
Skin infections, local wound infection, skin
breakdown, pneumonia, and urinary tract infections
occurring perioperatively may lead to seeding of the
prosthetic joint. Preoperative screening directed
toward the detection and correction of dental and
urogenital infection may limit the perioperative development of prosthetic joint infections. In the postoperative period, attention should be directed toward the
early detection of the infections that may seed the
joint, as noted above. Wound infections occurring in
the absence of prosthetic joint infection are generally
treated with systemic administration of antibiotics and
local drainage.
A number of changes in techniques and procedures have been associated with a decrease in the rate
of these early infections. Most studies, though, have
incorporated more than one change, making it difficult,
if not impossible, to attribute the decreased rate of
infections solely to a single modification.
The perioperative use of antibiotics is one
change that has been associated with a decrease in
early infections (2,12,41-43). During surgery, tissues
become devitalized, hematomas form, and cement
polymerization interferes with the body’s natural defenses. Bacteria introduced into these areas may grow
relatively unimpeded and remain sheltered from antibiotics that are subsequently administered. Because of
these considerations, it is generally agreed that, to be
effective, antibiotics should be administered prior to
incision of the skin, so that bactericidal levels of
antibiotics will be present in the surgical wound.
Although antibiotic therapy is often continued for days
after surgery, some studies suggest that once surgery
is completed, antibiotics can be discontinued without
increased rates of infection (4 1). Prolonged antibiotic
therapy may promote the emergence of resistant or-
ganisms and increase the likelihood of allergic reactions, as well as raise the total cost of the surgery.
The perioperative use of antibiotics has been
associated with early infection rates of 2% or less
(38,4143). First-generation cephalosporins are often
recommended, but few studies have compared them
with other antibiotics. It would seem reasonable to
adjust, if necessary, antibiotic(s) used, based on the
sensitivity of the bacteria at the individual center.
Other approaches to limiting early prosthetic
joint infection have been employed. Ultraclean filtered
air, laminar air flow, and ultraviolet lights appear to be
effective, according to the findings of some studies
(12,42,43). It is not clear, however, that these modalities significantly decrease the rate of prosthetic joint
infection when antibiotic prophylaxis is also employed. In a large study of the effects of laminar air
flow on the incidence of infection in patients who
underwent either total knee or total hip replacement
surgery without antibiotic prophylaxis, those in rooms
with laminar air flow actually showed an increased rate
of early prosthetic joint infection, but only in those
who had knee implants (42). It was suggested that
when total knee replacements were performed, the
operating room personnel were more likely to be
upstream from the patients, and shed bacteria would
seed the wound. When the operating room personnel
wore exhaust-ventilated suits, rates of early prosthetic
joint infection of both the hip and the knee were
decreased, even in patients who were not treated with
antibiotic prophylaxis. Antibiotic-impregnated cement
is being used in some centers, with success, in patients
with previous prosthetic joint infection (29,33). Concerns regarding prolonged toxicity and efficacy have
fueled the controversy regarding this technique (2,ll).
These observations indicate that appropriate
preoperative screening, referral to an experienced
surgical team, and prophylactic use of antibiotics at
the time of surgery will result in an acceptably low rate
of early prosthetic joint infection.
Late prosthetic joint infection. Late prosthetic
joint infections are usually due to hematogenous seeding of the joint. Most investigators have arbitrarily
distinguished these infections from those introduced
during surgery based on the time at which the infection
is initially detected. Early in their course, late prosthetic joint infections may be difficult to differentiate
from aseptic loosening of the implant. Pain is the
predominant symptom. Few patients have systemic
symptoms such as fever, and examination of the
infected joint may provide few clues to the diagnosis
(44). The use of radionuclide scans to distinguish
mechanical loosening from prosthetic joint infection
has not been generally accepted. Other imaging techniques, including computed tomography and nuclear
magnetic resonance, are of limited value or no value in
the differential diagnosis of mechanical versus infectious loosening of the implant. Joint aspiration or
bacteriologic examination at the time of replacement
of the “painful joint” prosthesis may be required to
establish the diagnosis.
Once seeding of the prosthetic joint has occurred, the likelihood of saving the prosthesis is not
very high (38,44). Patients with a longer duration of
symptoms prior to the institution of antibiotics, those
with inflammatory forms of arthritis such as RA, those
taking corticosteroids, and those infected with gramnegative organisms, particularly Pseudomonas, may
be more likely to require removal of the prosthesis
(38,45). Although a second prosthesis can be inserted
after removal of the infected prosthesis, the rate of
success with re-implantation is considerably less than
with initial implantation. Often, there is a delay in
excess of 6 months between the time of removal of the
first prosthesis and implantation of a replacement
prosthesis (46). Unsuccessful re-implantation, which
is not uncommon, may lead to joint fusion, creation of
an unstable joint, and occasionally, chronic osteomyelitis. The mortality associated with prosthetic joint
infection is not insignificant; rates as high as 20% have
been reported by different investigators (46,47).
Because of the devastating results associated
with these late prosthetic joint infections, a number of
health professionals have advocated the prophylactic
use of antibiotics in patients with prosthetic joints who
undergo procedures which might result in bacteremia
(25,48,49). Others, citing the relative avascular nature
of bone, the apparent requirement of large numbers of
bacteria to seed the joint, and the relative infrequency
of hematogenous seeding of prosthetic joints, have
suggested that the actual cost and risk of adverse
reactions related to the antibiotic outweigh any potential benefits (17,20,27,50).
Clearly, to resolve such a dilemma, large, multicenter studies of long duration are required. Unfortunately, such studies have not been performed. Lacking this information, any attempt to determine the role
of antibiotic prophylaxis requires addressing a number
of considerations. These include the rate at which
prosthetic joints become infected, whether certain
patients are at higher risk of infection, the outcome of
prosthetic joint infection, a clear definition of the
circumstances associated with bacterial seeding of
prosthetic joints, and the efficacy of antibiotic prophylaxis in preventing seeding of the prosthetic joint.
These considerations have to be balanced against the
cost and risk of antibiotic prophylaxis.
The number of patients with joint prostheses
who will develop late and, presumably, hematogenous-related infection is largely unknown. It seems
reasonable to assume that once a prosthetic joint is
implanted, the patient will be at risk of developing an
infection in that joint for the rest of his or her life. It is
also difficult to determine from most of the reported
studies which of the procedures a patient may undergo
will result in bacteremia of sufficient magnitude to seed
a joint. In one study, in which antibiotic prophylaxis
was not used, 1,000 patients with 1,112 prosthetic
joints were followed for an average of 6 years; there
were 11 late prosthetic joint infections, yielding an
annual rate of 0.18% (18). Other investigators have
suggested that the annual rate may be at least 3 times
as high (0.60%) (51). Does the duration of time that a
prosthesis is in place alter the incidence of infection?
With time and wear, prosthetic joints tend to loosen.
Loosening may be associated with inflammation, provoked by metal joint fragments and increased vascular
supply. This may increase the likelihood of bacteremic
seeding. There are no studies addressing this concern.
Another consideration is whether certain patients are at higher risk for late hematogenous seeding
of the prosthetic joint. Patients with RA have evidence
of chemotactic and phagocytic dysfunction, are often
taking immunomodulatory drugs, and may have more,
and possibly longer, episodes of bacteremia. Several
studies have demonstrated that both early and late
prosthetic joint infection are more likely to occur in
patients with RA. The risk of prosthetic joint infection
in RA patients has been reported to be I S % , and can
possibly be as high as 4.2 times the rate in patients
without RA (51). In another study, though of relatively
small numbers of patients, all who developed prosthetic joint infection more than 3 years after surgical
implantation had RA (38).
A third, and critical, consideration is whether
the circumstances associated with late prosthetic joint
infection can be identified. A number of reports which
have included a list of bacteria isolated from the
infected joint have shown that an established infection
elsewhere in the body may seed the prosthetic joint
(10,16,18,13). In cases of established pneumonia, skin
infection, or genitourinary infection, it would seem
prudent to treat these disorders early and vigorously
with antibiotics.
Consideration of the bacteria isolated from late
infection of the prosthetic joint gives some clues to the
possible source. Late infections are often caused by
Staphylococcus aureus or Staphylococcus epidermidis
(44), with as many as 53% of late infections associated
with these organisms (25). Bacterial isolates compatible with a dental source can be found in 6 1 3 % of the
cases of late prosthetic joint infection (25,46,47,51). In
as many as 25%, a source was not identified. In those
situations, prevention would obviously be difficult.
Can the prophylactic utilization of antibiotics
prevent late prosthetic joint infection? If so, it remains
to be determined which antibiotic should be used and
for which types of procedures. Little and Jasper have
argued that since staphylococci were responsible for
most cases of late prosthetic joint infection, a cephalosporin would be the drug of choice for antibiotic
prophylaxis (17,20). However, based on the organisms
associated with late infection, they also stated that
prosthetic joint seeding during “routine” dental work
was extraordinarily rare and did not require antibiotic
prophylaxis. It would seem that these arguments are
mutually exclusive. Can “routine” dental work be
separated a priori from more invasive dental work as
being likely to seed a joint? Since the exact conditions
responsible for late prosthetic joint infection have not
been clearly identified, this seems unlikely. Furthermore, there is little information to support the concept
that if antibiotic prophylaxis were to be used, then an
agent geared toward eradication of organisms not
generally found in the oral cavity should be employed.
Even less is known about such prophylaxis for elective
genitourinary or gastrointestinal tract procedures.
Given this dearth of factual information, can
any recommendations be made regarding prophylaxis
for late prosthetic joint infection? From their analysis
concentrating on fatal outcomes, Jacobson et a1 concluded that antibiotic prophylaxis for dental procedures was not justified (27). Their recommendations
were based on the assumptions that the risk of hematogenous infection is only 0.7%, that only 6% of the
infections are dentally related, and that the mortality
associated with such an occurrence is approximately
6.5%. They estimated that for one million dental visits,
there would be 4.86 deaths or amputations attributable
to infection of the prosthetic joint. These estimates
seem exceedingly low. The drug reactions that might
occur with prolonged antibiotic use in such patients
were not included in their analysis. However, assum-
ing that penicillin would prevent only 27% of dental
visit-associated prosthetic joint infections, there
would be an estimated 4.45 deaths or amputations.
They assumed that by using cephalexin, 85% of these
infections would be prevented and only 1.21 deaths or
amputations would occur. Arguing that 400 and 200
“severe” reactions (not fatal, but yet, not defined by
the authors) to penicillin and cephalexin, respectively,
could be expected, they concluded that antibiotic
prophylaxis for dental treatment was not an effective
strategy. Not factored into this analysis was the pain
and limitation associated with prosthetic joint infection. It is likely that the authors did not consider the
probability that patients with prosthetic joints have
previously received antibiotics and may therefore be
at less risk of developing an antibiotic-associated fatal
reaction. Finally, the rate of occurrence of an antibiotic reaction related to parenteral or prolonged use and
the risk of serious reaction may have been overestimated.
Norden, who examined the economic cost of
late prosthetic joint infection (19), assumed an annual
risk of prosthetic joint infections associated with dental procedures to be 0.03%. Considering a cost of $15
for antibiotic prophylaxis and assuming that 1 dental
visit per year would require such prophylaxis, the
annual cost to 100,000 patients would $15 million. At
$30,000 per infection, the cost of therapy for the
estimated 30 dental procedure-associated prosthetic
joint infections would be $900,000.
Calculations can also be performed based on
arguments similar to those in the published reports,
but with markedly different results. If one assumes
that the risk of late prosthetic joint infection is 0.18%
annually and that 12% of the infections are related to
dental procedures, then 216 dental-associated prosthetic joint infections per million patient-years at risk
would be expected. Assuming an 18% mortality rate,
there would be 39 deaths. Estimating that therapy for
1 such infection would cost $50,000, the total cost
would be $10.8 million. If prophylaxis was employed
using 1 gm of cephalexin prior to a procedure and two
500-mg doses afterwards, and assuming that 85% of
dental-associated prosthetic joint infections would be
prevented, then there would be 32 infections and
deaths (6 infection associated, 1 antibiotic associated).
If, instead, 1 gm of penicillin V potassium followed by
two 500-mg doses were used, and assuming that oral
penicillin would provide protection comparable with
that of cephalexin, a similar number of infections and
infection-related deaths would be observed.
Table 1. Risk factors for prosthetic joint infections
Early infection
Late infection
Prolonged duration of surgery
Number of operating room personnel
Inexperienced primary surgeon
Advanced age
Rheumatoid arthritis
Perioperative nonarticular infections
Type of prosthesis
Rheumatoid arthritis
Nonarticular infections
Duration of implant (?)
Loosening of implant (?)
Based on 1.5 dental visits per patient per year,
fatal anaphylaxis (assuming 9 such reactions per 10
million events) might be expected in 1.35 patients. The
cost of prophylaxis (medication plus treatment of
unprevented prosthetic joint infection) would be $8.95
million dollars, based on costs at our institution ($4.90
per course of prophylaxis with either penicillin V
potassium or cephalexin and $50,000 per prosthetic
joint infection).
The risk factors associated with both early and
late prosthetic joint infection are shown in Table 1; the
estimated cost of antibiotic prophylaxis is shown in
Table 2.
Practice patterns among health care
In many situations in which there are few data
to make clear decisions about therapy, medical practice is often based upon local standards of care. We
have recently surveyed rheumatologists, orthopedic
surgeons, primary care practitioners, and dentists in
the state of Alabama (32). Listings of these practitioners were obtained from the corresponding state professional associations. Since there were fewer than 100
rheumatologists and orthopedic surgeons who practiced in Alabama, all were surveyed. Because of the
large number of primary care practitioners and dentists practicing in Alabama, a 10% random sample was
believed to be adequate and representative of the
entire Alabama membership for these 2 professional
A questionnaire including demographic and
general practice patterns for these practitioners was
developed. The questionnaire and a prepaid return
envelope were mailed to the practitioners. Physicians
and dentists were asked to give their recommendations
for prophylaxis in 4 situations: prior to dental, genitourinary, and gastrointestinal procedures and prior to
surgery of infected tissues. Overall, 163 professionals
responded to the survey (response rate of 40.5%). One
of every 3 practitioners had known or had treated a
patient who had a prosthetic joint infection during the
year before the survey. These same practitioners were
also asked about their practice patterns for the same 4
clinical events in patients with prosthetic heart valves.
Although this questionnaire was not formally tested
for internal and external reliability, the questions were
clearly formulated, and a “yes” or “no” answer was
anticipated; thus, it very likely represents the actual
practice patterns of these health professionals.
The overall reported use of antibiotic prophylaxis for patients with prosthetic joints was 60.5%; the
lowest was for gastrointestinal procedures (53.9%),
and the highest was for surgery on contaminated
tissues (68.1%). These rates also varied among the
different practitioners: the lowest among the primary
care practitioners (35.6%), and the highest among the
orthopedic surgeons (87.8%). In contrast, the same
practitioners would use antibiotic prophylaxis for dental procedures in patients with prosthetic heart valves
81-100% of the time, for genitourinary and gastrointestinal procedures 79.3-90% of the time, and for
surgery on infected tissues 65.9-100% of the time.
When the patterns of prophylactic use of antibiotics
for these 4 clinical events were compared between
patient groups, the differences were statistically significant (P < 0.001) among all groups of practitioners,
except for the orthopedic surgeons, who used antibiotic prophylaxis with a similar frequency in both
groups of patients. Because orthopedic surgeons are
more likely to be the group who actually performs the
joint replacement surgery, they are also more likely to
be treating a patient with a prosthetic joint infection,
and, thus, report a higher rate of prophylactic use of
We also surveyed a random sample of RA
Table 2. Estimated risk (per million patient-years) and annual cost
(in millions of dollars) of infection or death in patients with prosthetic joints undergoing dental procedures*
Antibiotic prophylaxis
Risk of infection
Risk of death
cost ($1
* Estimates are based on the following assumptions: annual risk =
0.18% (or 1,80O/year);dental-associated = 12.0% (or 216/year); cost
of therapy for prosthetic joint infection = $50,000; cost of cephalexin or penicillin V potassium = $4.90; protection with antibiotics =
85%; dental visitdyear = 1.5; fatal anaphylaxis = 0.9/million. Costs
are 1990 dollars for The University of Alabama Hospital.
patients who receive followup care at our institution.
A questionnaire pertaining to the use of antibiotics for
the same procedures as described in the questionnaire
to the health practitioners was used. A trained research assistant conducted the interview by telephone.
Of the 80 patients interviewed, only 10% indicated that
they had been made aware of any recommendations
for the prophylactic use of antibiotics (32). It should
also be noted that 8 of these patients had experienced
a joint infection. Three of these infections had occurred in prosthetic joints, and in 1 instance, it was
clearly associated with a procedure known to be
associated with bacteremia.
Several other surveys inquiring into orthopedists’ recommendations regarding the prophylactic use
of antibiotics have been performed. In one study, with
604 orthopedic surgeons responding (36% response
rate), 41% concluded there was an association between bacteremia and prosthetic joint infection; 93%
thought that antibiotic prophylaxis was indicated, and
most recommended a cephalosporin (20). In still another survey of 177 orthopedic residency programs,
from which there were 107 responses (60%), 89%
recommended prophylactic use of antibiotics, and as
in the other survey, a cephalosporin was favored (48).
Even though our survey was conducted in Alabama,
and in a strict sense, its results cannot be extrapolated
to the entire US population, it nevertheless demonstrates a difference in practice patterns between orthopedic surgeons and other health professionals. The
other surveys (20,48), showed that practice patterns
were similar among orthopedic surgeons, at least in
regard to antibiotic prophylaxis, which suggests that
the results of our survey are not likely unique to the
state of Alabama.
Conclusions and recommendations
Based primarily on the review of available
information and, to a lesser extent, on our own experience, we give our recommendations for antibiotic
usage in patients with prosthetic joints. Whereas some
of the recommendations can clearly be supported by
published reports, others are based on our interpretation of the literature and our clinical judgment.
Patients being considered for joint replacement
surgery should undergo preoperative screening for the
presence of infection at potential sources of seedingdental, genitourinary, gastrointestinal, or cutaneous.
Any such infections should be corrected prior to
surgery. Dental hygiene should be emphasized to limit
postoperative problems. Medications with the potential to compromise normal host-bacteria interactions
should be tapered to the minimal acceptable dosage or,
preferably, discontinued prior to surgery.
When antibiotics are used perioperatively, the
initial doses should be timed so that bactericidal levels
are present at the time of surgery. Other strategies
(ultraclean air, small-weave surgical garb, etc .) may
further reduce the risk of early prosthetic joint infection, but such techniques cannot be uniformly recommended at this time.
Bacterial infections occurring in patients with a
prosthetic joint should be rapidly diagnosed and appropriately treated, which would include surgery of
infected tissue. As a corollary to this, the patient with
a joint prosthesis should be informed of the need for
this kind of surveillance and aggressive treatment.
Patients at high risk of developing an infection
in the prosthetic joint or those likely to have a poor
outcome associated with such a development (i.e.,
patients with RA or other chronic debilitating disease,
or those taking immunomodulatory drugs) should receive antibiotics before any procedure that is likely to
result in bacteremia. The antibiotic to be used for
prophylaxis depends on the type of procedure and the
patient’s history of drug allergies.
The prophylactic use of antibiotics in other
patients should be determined by the physician after
an analysis of the cost-benefit ratio of such a practice
in the physician’s own community. Reasonable estimates of the cost and risk of a hematogenous infection
of the prosthetic joint and of antibiotic prophylaxis can
be obtained in a manner similar to that described in
Table 2, but using local data. Until data from randomized clinical trials are published, these estimates,
paired with sound clinical judgment, should guide a
physician in dealing with the patient with a prosthetic
joint who undergoes procedures that are likely to
result in bacteremia. Based on our experience, we
routinely use antibiotic prophylaxis for all our rheumatoid arthritis patients with prosthetic joints undergoing such procedures.
We thank Janet Austin for conducting the patient
interviews and Brenda K. Bunn and Donna R. Haffner for
their expert secretarial assistance.
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Reminder to Contributors
A list of key words is provided in the January and July issues. Please refer to this list when
choosing key words for an article.
The Notes to Contributors includes the new requirement of subheads to be used in
abstracts. Abstracts should now be divided into the following sections: Objective, Methods, Results,
and Conclusion.
Manuscripts for publication, letters, news, and notes should be sent to: Peter H. Schur, MD,
Editor, Arthritis and Rheumatism, Arthritis and Rheumatism Editorial Off ice, Room 422, Richardson
Fuller Building, 221 Longwood Avenue, Boston, MA 021 15.
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