Periprosthetic Joint Infection
The Incidence, Timing, and Predisposing Factors
Luis Pulido MD, Elie Ghanem MD, Ashish Joshi MD, MPH,
James J. Purtill MD, Javad Parvizi MD, FRCS
Received: 30 August 2007/Accepted: 25 February 2008/Published online: 18 April 2008
? The Association of Bone and Joint Surgeons 2008
challenging complications of joint arthroplasty. We iden-
tified current risk factors of periprosthetic joint infection
after modern joint arthroplasty, and determined the inci-
dence and timing of periprosthetic joint infection. We
reviewed prospectively collected data from our database on
9245 patients undergoing primary hip or knee arthroplasty
between January 2001 and April 2006. Periprosthetic joint
infections developed in 63 patients (0.7%). Sixty-five
percent of periprosthetic joint infections developed within
the first year of the index arthroplasty. The infecting
organism was isolated in 57 of 63 cases (91%). The
most common organisms identified were Staphylococcus
aureus and Staphylococcus epidermidis. We identified the
following independent predictors for periprosthetic joint
infection: higher American Society of Anesthesiologists
score, morbid obesity, bilateral arthroplasty, knee arthro-
myocardial infarction, urinary tract infection, and longer
hospitalization. This study confirmed some previously
implicated factors and identified new variables that predis-
pose patients to periprosthetic joint infection.
Level of Evidence: Level II, prognostic study. See the
Guidelines for Authors for a complete description of levels
Periprosthetic joint infection is one of the most
Total joint arthroplasty is a safe and effective procedure
improving the quality of life and restoring function to
patients with arthritis of the hip and knee [4, 6, 8]. Although
its general success is beyond dispute, postoperative com-
plications such as periprosthetic joint infection (PJI) still
occur. Currently, PJI is an important mechanism of implant
failure and need for revision arthroplasty [3, 18, 20].
Numerous challenges may be associated with PJI that
can include the need for multiple operations, a long period
of disability for the patient, and, occasionally, suboptimal
outcome [2, 17]. In the elderly, PJI may result in a higher
incidence of mortality .
Although the use of prophylactic antibiotics and other
strategies such as the use of body exhaust systems and
laminar airflow in the operating room have helped reduce
the incidence of PJI [12, 13], they have not eliminated the
risk. It has been projected that the incidence of PJI may be
increasing . Because of the economic and psychologic
burden of this complication, strategies to minimize or
prevent PJI may be needed. Therefore, continuous effort
and research are necessary to help reduce its incidence to a
minimum. We believe identification of the current risk
factors that predispose patients to deep periprosthetic joint
infection after modern hip and knee arthroplasties will help
establish simple strategies to avoid them. We presumed
modern-day risk factors (Table 1) for PJI might differ from
those previously described.
We therefore had two objectives: First to identify cur-
rent risk factors of periprosthetic joint infection after
modern joint arthroplasty, and second to determine the
incidence and timing of periprosthetic joint infection. We
also report our experience with the current causative
organisms and initial management of PJI.
One of the authors (JP) is a consultant for Stryker Orthopaedics.
Each author certifies that his or her institution has approved the
human protocol for this investigation and that all investigations were
conducted in conformity with ethical principles of research.
L. Pulido, E. Ghanem, A. Joshi, J. J. Purtill, J. Parvizi (&)
Rothman Institute of Orthopedics, Thomas Jefferson University
Hospital, 925 Chestnut Street, Philadelphia, PA 19107, USA
Clin Orthop Relat Res (2008) 466:1710–1715
Materials and Methods
We performed a retrospective cohort study using pro-
spectively collected data from our arthroplasty database;
patients were not recalled for this study. We identified
9245 patients undergoing primary hip or knee arthroplasty
between January 2001 and April 2006. Of these, 7739
patients underwent unilateral joint arthroplasty, and 1496
had simultaneous bilateral surgery. Primary hip arthro-
plasty was performed in 5060 patients, including 4635
unilateral surgeries, and 425 simultaneous bilateral hip
replacements. Primary knee arthroplasty was performed in
4185 patients, including 3114 unilateral procedures and
1071 bilateral total knee replacements. There were 3882
males with a mean age of 62 years (range, 15–94 years)
and 5363 females with a mean age of 66 years (range, 14–
97 years). The minimum followup was 12 months (mean,
43 months; range 12–76 months). We did not have infor-
mation regarding the number of patients lost to followup
before the 12-month minimum followup.
The protocols for infection prophylaxis were the same
throughout the study period. This included administration
of intravenous antibiotic within 1 hour of the arthroplasty
and for 24 hours postoperatively. We performed all
arthroplasties in operating rooms equipped with vertical
laminar flow with all members of the surgical team wearing
helmet aspirator suits. Neuraxial anesthesia was used for all
surgeries unless contraindicated. We placed patients in the
supine position for surgery. Skin preparation included the
use of alcohol and iodine lavage plus an Incise adhesive
drape (3MTMIobanTM, St. Paul, MN). We routinely used
double gloves for all procedures.
We performed hip arthroplasty through a modified
anterolateral approach using uncemented components in all
cases. Knee arthroplasty was performed under tourniquet
using a medial parapatellar arthrotomy approach. We used
cemented fixation for all knees. No drains were used in any
of the cases.
Postoperative wound management consisted of appli-
cation of a sterile dressing, which was placed over the
incision in the operating room and usually kept for
48 hours. We then inspected the wound and changed the
sterile gauze twice daily until the patient was discharged
from the hospital.
The prophylactic anticoagulation regimen consisted of
administration of warfarin on postoperative Day 1 and
continuing for 6 weeks, aiming for an international nor-
malized ratio of 1.5 to 2.0. Unless contraindicated, patients
also received 1000 units of intravenous heparin at the time
of dislocation of the hip or before inflation of the tourniquet
during knee arthroplasty. Patients’ comorbid conditions or
postoperative cardiovascular complications altered the
chemoprophylaxis protocol in some cases, which included
administration of intravenous or subcutaneous heparin for
patients with arrhythmia or cardiac disease.
We followed patients at 6 weeks, 6 months, 2 years, and
5 years after surgery. They are encouraged to contact their
surgeon as needed or in the presence of fever, wound
drainage, or any unexpected adverse event. We prescribed
antibiotic prophylaxis before dental procedures (600 mg
clindamycin orally) to all patients at their first followup,
which was recommended during the first 2 years after
The diagnosis of deep periprosthetic infection was made
if at least three of the following five criteria were present:
(1) abnormal serology (erythrocyte sedimentation rate[
30 mm/hour; C-reactive protein[1 mg/dL); (2) strong
clinical and radiographic suspicion for periprosthetic
Table 1. Continuous and categorical variables used to identify possible predictors of joint infection
Demographic factors: Gender, age, ethnicity, height, weight, body mass index
Patient medical factors: American Society of Anesthesiologists score, alcohol abuse, hypertension, hyperlipidemia, diabetes mellitus, rheumatoid
arthritis, cardiac arrhythmias, coronary heart disease, peripheral vascular disease, congestive heart failure, cardiac transplant, cardiac valvular
disease, dementia, stroke, neurologic disease (paralysis, dyskinesia, Parkinson), renal insufficiency, renal failure and dialysis, anemia (aplastic,
autoimmune, iron deficiency), coagulopathy, urinary tract infection, liver disease (hepatitis B, hepatitis C, hepatic insufficiency), malignancy
(all visceral, metastatic and melanoma), tuberculosis, venous thromboembolic disease
Preoperative laboratory values: Hemoglobin, international normalized ratio (INR), leukocyte count, glucose, creatinine, albumin
Surgical and postoperative variables
Surgery: Joint operated (hip versus knee), side (unilateral, simultaneous bilateral), operative time (minutes)
Blood management: Transfusion (yes or no, number of units transfused, type of transfusion—allogenic versus autologous)
Postoperative laboratory values: Hemoglobin, INR, leukocyte count, glucose, creatinine, albumin
Postoperative medical complications: Urinary tract infection, pneumonia, Clostridium difficile-associated diarrhea, pulmonary embolism, acute
myocardial infarction, arrhythmia, congestive heart failure, atrial fibrillation, stroke, deep venous thrombosis, lung aspiration, fever
Postoperative local complications: Cellulitis, hematoma, wound infection, wound drainage, wound dehiscence, blisters, vascular injury,
compartment syndrome, dislocation
Volume 466, Number 7, July 2008Periprosthetic Joint Infection 1711
infection such as periosteal elevation, focal osteolysis, hot
and swollen joint, draining sinus, (3) positive joint
aspiration culture; (4) evidence of purulence during the
subsequent surgical intervention; and (5) a positive
intraoperative culture .
We performed descriptive analysis using univariate
statistics on a large number of variables (Table 1). Patients
were included only once in the analysis even though some
patients received multiple surgeries. All continuous vari-
ables are reported as means and standard deviations. We
compared potential predictive variables between the two
groups of patients (with or without deep periprosthetic
infection) using parametric (t statistics) or nonparametric
statistics (Wilcoxon) as appropriate. We reported categor-
ical variables as frequency distribution and comparisons
were made using parametric (chi square statistics) and
nonparametric statistics (Fisher’s exact). We kept variables
significant at p = 0.10 in the final statistical model using
stepwise logistic regression. Multivariate analysis then was
performed using selection stepwise logistic regression after
adjusting for the potential confounders to determine note-
worthy predictors of periprosthetic infection. Confounders
included the following: race, physical status score (ASA),
body mass index, rheumatoid arthritis, venous thrombo-
embolism, anemia, hypercholesterolemia, dementia, knee
arthroplasty, simultaneous bilateral surgery, operative
time, hospital length, postoperative creatinine, allogenic
transfusion, postoperative atrial fibrillation, postoperative
myocardial infarction, postoperative urinary tract infection,
Variables were considered clinically important predictors of
periprosthetic infection with a p\0.05 after adjusting for
tailed and at an alpha level of 0.05. All results have been
reported as 95% confidence intervals and p values.
Periprosthetic infection was diagnosed in 63 of 9245
patients, representing an overall incidence of 0.7%
(Table 2). Infection developed after hip arthroplasties in 15
patients and after knee arthroplasties in 48 patients
accounting for an incidence of 0.3% (15 of 5060) and 1.1%
(48 of 4185), respectively (p\0.0001). The majority of
PJI (65% [41 of 63 infections]) were diagnosed within the
first year after surgery. Twenty-seven percent of the
infections were diagnosed during the first 30 days after
arthroplasty (17 patients). The average time to diagnosis
of PJI was 431 days after the index surgery (range,
11–1699 days). Infection was classified as chronic late in
35 patients (56%), acute or early in 20 patients (31%), and
as acute hematogenous in eight patients (13%).
The organism was isolated in 91% of the cases (57 of
63). Clustered gram-positive cocci were the most common
infecting organisms. The isolated organisms in the order
of frequency were methicillin-resistant Staphylococcus
aureus (19%), methicillin-sensitive S. aureus (19%),
methicillin-resistant Staphylococcus epidermidis (11%),
and methicillin-sensitive S. epidermidis (8%). Fifty-three
percent of the Staphylococcus organisms were methicillin-
Table 2. Details of periprosthetic joint infection in the cohort
Description Total jointKnee
Number of patients924541855060
Mean time to diagnosis
I. Acute20 (31.7%) 14 (30%)6 (40%)
II. Chronic 35 (55.6%) 29 (60%)6 (40%)
III. Acute hematogenous8 (12.7%)5 (10%)3 (20%)
Microorganism 63 4815
Streptococcus pneumoniae 11
+ E. faecalis
+ K. pneumoniae
MRSA + MSSA11
MRSE + Enterococcus
MRSA = Methicillin-resistant
Methicillin-sensitive S. aureus; MRSE = Methicillin-resistant Staph-
ylococcus epidermidis; Methicillin-sensitive S. epidermidis.
1712Pulido et al.Clinical Orthopaedics and Related Research
resistant. Gram-negative bacteria were isolated in seven
joints (11%); Escherichia coli and Klebsiella pneumoniae
were the most prevalent organisms. Polymicrobial infec-
tion was diagnosed in four patients (Fig. 1).
The majority (63%) of the PJIs initially were treated
with two-stage exchange arthroplasty. We performed irri-
gation and de ´bridement in 21 patients (33%). Two patients
(4%) underwent one-stage reimplantation.
Unadjusted univariate analysis presented multiple vari-
ables associated with PJI (Table 3). After multivariable
logistic regression analysis, we found the following inde-
pendent predictors of PJI after primary joint arthroplasty:
higher American Society of Anesthesiologists score ([2),
morbid obesity (body mass index[40 kg/m2), simulta-
neous bilateralsurgery (compared
procedures), TKA (compared with THA), transfusion of
allogenic blood units, postoperative atrial fibrillation,
myocardial infarction, urinary tract infection, and longer
hospitalizations (mean of 5 days hospitalization) (Table 4).
Deep periprosthetic infection is one of the most common
causes of implant failure and revision surgery [3, 18, 20],
with dramatic medical and socioeconomic implications.
Although implementation of standardized strategies such as
a clean air operating room, adequate administration of per-
ioperative antibiotics, and body exhaust systems have
contributed to decrease this complication, periprosthetic
infection still continues to occur after total joint arthropla-
sties [3, 5, 13]. Identification of patients at high risk for PJI
establishing adequate measurements to help prevent it.
There are some weaknesses of our study. First, this is a
retrospective cohort study subject of variability in data
collection. However, the prospective nature of our data
Fig. 1 Classification and infec-
periprosthetic joint infections
are shown. Methicillin-resistant
Staphylococcus aureus (MRSA),
methicillin-sensitive S. aureus
S. epidermidis (MSSE).
Table 3. Predisposing factors for periprosthetic joint infection*
Patient preoperative factors
American Society of Anesthesiologists[2
Higher body mass index
Longer operative time
Longer hospital stay
Allogenic blood transfusion
Urinary tract infection
*univariate, unadjusted analysis.
Volume 466, Number 7, July 2008Periprosthetic Joint Infection 1713
collection probably helped reduce recall and selection bias
to our analysis. Second, because of the relatively low
incidence of events (PJI), the analysis may have failed to
detect the significance of some factors. However, it is
based on a relatively large cohort of patients undergoing
primary arthroplasty in one institution and with all patients
subjected to the same care protocols. Third, because it was
not our intention to report the all-time incidence of PJI, but
merely to follow the patients for a minimum of 1 year, the
true incidence of PJI in this cohort is likely underestimated.
Finally, we are aware the multivariate model is more
appropriate of the two models. However, we provided the
results of our initial unadjusted analysis (Table 3), because
that provides all possible important variables associated
with infection from among those we studied.
We confirmed some previously implicated risk factors
such as wound drainage, hematoma formation, history of
rheumatoid arthritis, longer operative time, and urinary
tract infection [1, 12–14, 19, 21] remain as important
predisposing factors for modern PJI. We also identified
new risk factors that, to our knowledge, have not been
linked to PJI previously [1, 12–14, 16, 19, 21]. However, to
remove the influence of confounding variables, we per-
formed multivariate analysis to identify the independent
factors (Table 4). Among these independent factors was
the development of postoperative atrial fibrillation and
myocardial infarction. It is intriguing why such medical
complications should predispose the patients to PJI. One
plausible explanation is all patients with serious cardiac
complications receive aggressive anticoagulation with
heparin or similar agents. Use of aggressive anticoagula-
tion has been reported as an independent risk factor for
development of PJI . Another explanation is these
complications develop in patients who generally are sicker
and older with preexistent medical conditions that would
retard wound healing resulting in later infection.
Yet another important risk factor for development of PJI
was longer hospital stay. Longer hospital stay was an
independent risk factor even after adjusting for age,
previous medical comorbidities, wound problems, and
development of medical complications. One may hypoth-
esize that with a longer hospital stay, patients were more
likely exposed to nosocomial and virulent organisms that
could result in later PJI. In fact, the large incidence of PJI
by resistant organisms may relate partly to this factor.
Our data confirm transfusion with allogenic blood is an
independent risk factor for having PJI develop. Patients
receiving allogenic transfusion were 2.1 times more likely
to have PJI develop compared with patients receiving no
transfusion. The association between allogenic transfusion
and infection has been reported and relates to the immu-
nomodulation effect of the transfusion . Among other
important risk factors, and in line with a previous study by
Wilson et al., the presence of urinary tract infection and
obesity is also important .
Based on the findings of our study, we have instituted
stringent preoperative protocols that aim to minimize these
risk factors. For example, for patients with a history of
urinary tract infection or at high risk, we have instituted
preoperative screening. If urinary infection is confirmed,
the patients will receive appropriate antibiotic therapy and
the infection will be eradicated before proceeding with
joint arthroplasty. Another important protocol relates to
blood conservation. Autologous blood donation is offered
to all of our patients undergoing hip arthroplasty and par-
ticularly encouraged for patients awaiting bilateral hip
arthroplasties. We reserve bilateral joint arthroplasties for a
select group of patients with minimal comorbidities. Knee
arthroplasty is performed under tourniquet to minimize
operative blood loss and all exposed tissue is cauterized
gently to prevent postoperative hematoma formation. Other
efforts used to prevent postoperative hematoma formation
include meticulous hemostasis and the use of drain in cases
with large dead space. In addition, we attempt to minimize
the need for postoperative transfusion by screening and
correcting, whenever possible, the preoperative anemia.
Table 4. Independent predisposing factors for periprosthetic joint infection*
Independent factorsSlope Standard errorOdds ratio95% Confidence interval p Value
Body mass index[40 kg/m2
American Society of Anesthesiologists[2
Simultaneous bilateral surgery
1.17 0.363.23 1.6–6.5 0.001
0.002 TKA 1.050.342.85 1.5–5.6
Allogenic blood transfusion0.75 0.312.11 1.1–3.90.02
Postoperative atrial fibrillation 1.830.786.22 1.4–28.5 0.02
Postoperative myocardial infarction3.02 1.1620.4 2.1–199.90.009
Postoperative urinary infection 1.7 0.845.45 1.0–8.70.04
Longer hospital stay 0.090.02 1.09 1.0–1.1 0.0003
*multivariate, adjusted analysis.
1714 Pulido et al.Clinical Orthopaedics and Related Research
Some patients may be candidates for erythropoietin therapy Download full-text
before surgery. We also refrain from administering blood
transfusion based on hemoglobin values and proceed with
transfusion for symptomatic patients only. Patients who
have atrial fibrillation or myocardial infarction now receive
controlled anticoagulation without boluses per new proto-
it is possible and safe to do so. We continue to implement
strict sterile techniques and other proven methods such as
adequate antibiotic prophylaxis to minimize PJI.
We believe PJI will continue to present a major challenge
for the medical community in the future. Effective strate-
gies to minimize risk factors identified in this and previous
studies should be implemented if the incidence of this
complication is to be reduced.
1. Berbari EF, Hanssen AD, Duffy MC, Steckelberg JM, Ilstrup DM,
Harmsen WS, Osmon DR. Risk factors for prosthetic joint
infection: case-control study. Clin Infect Dis. 1998;27:1247–1254.
2. Bozic KJ, Katz P, Cisternas M, Ono L, Ries MD, Showstack J.
Hospital resource utilization for primary and revision total hip
arthroplasty. J Bone Joint Surg Am. 2005;87:570–576.
3. Clohisy JC, Calvert G, Tull F, McDonald D, Maloney WJ.
Reasons for revision hip surgery: a retrospective review. Clin
Orthop Relat Res. 2004;429:188–192.
4. Felson DT, Lawrence RC, Hochberg MC, McAlindon T, Dieppe
PA, Minor MA, Blair SN, Berman BM, Fries JF, Weinberger M,
Lorig KR, Jacobs JJ, Goldberg V. Osteoarthritis: new insights.
Part 2: treatment approaches. Ann Intern Med. 2000;133:726–
5. Garvin KL, Hanssen AD. Infection after total hip arthroplasty:
past, present, and future. J Bone Joint Surg Am. 1995;77:1576–
6. Jones CA, Beaupre LA, Johnston DW, Suarez-Almazor ME.
Total joint arthroplasties: current concepts of patient outcomes
after surgery. Clin Geriatr Med. 2005;21:527–41, vi.
7. Kurtz S, Ong K, Lau E, Mowat F, Halpern M. Projections of
primary and revision hip and knee arthroplasty in the United
States from 2005 to 2030. J Bone Joint Surg Am. 2007;89:
8. Lavernia CJ, Guzman JF, Gachupin-Garcia A. Cost effectiveness
and quality of life in knee arthroplasty. Clin Orthop Relat Res.
9. McGarry SA, Engemann JJ, Schmader K, Sexton DJ, Kaye KS.
Surgical-site infection due to Staphylococcus aureus among
elderly patients: mortality, duration of hospitalization, and cost.
Infect Control Hosp Epidemiol. 2004;25:461–467.
10. Parvizi J, Ghanem E, Joshi A, Sharkey PF, Hozack WJ, Rothman
RH. Does ‘‘excessive’’ anticoagulation predispose to peripros-
thetic infection? J Arthroplasty. 2007;22(suppl 2):24–28.
11. Parvizi J, Ghanem E, Menashe S, Barrack RL, Bauer TW.
Periprosthetic infection: what are the diagnostic challenges?
J Bone Joint Surg Am. 2006;88(suppl 4):138–147.
12. Peersman G, Laskin R, Davis J, Peterson M. Infection in total
knee replacement: a retrospective review of 6489 total knee
replacements. Clin Orthop Relat Res. 2001;392:15–23.
13. Phillips JE, Crane TP, Noy M, Elliott TS, Grimer RJ. The inci-
dence of deep prosthetic infections in a specialist orthopaedic
hospital: a 15-year prospective survey. J Bone Joint Surg Br.
14. Poss R, Thornhill TS, Ewald FC, Thomas WH, Batte NJ, Sledge
CB. Factors influencing the incidence and outcome of infection
following total joint arthroplasty. Clin Orthop Relat Res.
15. Raghavan M, Marik PE. Anemia, allogenic blood transfusion,
and immunomodulation in the critically ill. Chest. 2005;127:
16. Saleh K, Olson M, Resig S, Bershadsky B, Kuskowski M, Gioe T,
Robinson H, Schmidt R, McElfresh E. Predictors of wound
infection in hip and knee joint replacement: results from a
20 year surveillance program. J Orthop Res. 2002;20:506–515.
17. Segawa H, Tsukayama DT, Kyle RF, Becker DA, Gustilo RB.
Infection after total knee arthroplasty: a retrospective study of the
treatment of eighty-one infections. J Bone Joint Surg Am.
18. Sharkey PF, Hozack WJ, Rothman RH, Shastri S, Jacoby SM.
Insall Award paper. Why are total knee arthroplasties failing
today? Clin Orthop Relat Res. 2002;404:7–13.
19. Surin VV, Sundholm K, Ba ¨ckman L. Infection after total hip
replacement: with special reference to a discharge from the
wound. J Bone Joint Surg Br. 1983;65:412–418.
20. Vessely MB, Whaley AL, Harmsen WS, Schleck CD, Berry DJ.
The Chitranjan Ranawat Award: Long-term survivorship and
failure modes of 1000 cemented condylar total knee arthropla-
sties. Clin Orthop Relat Res. 2006;452:28–34.
21. Wilson MG, Kelley K, Thornhill TS. Infection as a complication
of total knee-replacement arthroplasty: risk factors and treatment
in sixty-seven cases. J Bone Joint Surg Am. 1990;72:878–883.
Volume 466, Number 7, July 2008Periprosthetic Joint Infection1715