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Infection After Primary Total Hip Arthroplasty

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 n Review Article

Instructions
1. Review the stated learning objectives at the beginning
of the CME article and determine if these objectives match
cme
ARTICLE
your individual learning needs.
2. Read the article carefully. Do not neglect the tables
and other illustrative materials, as they have been selected to

Infection After Primary Total

enhance your knowledge and understanding.
3. The following quiz questions have been designed to
provide a useful link between the CME article in the issue

Hip Arthroplasty
and your everyday practice. Read each question, choose
the correct answer, and record your answer on the CME
Registration Form at the end of the quiz.
4. Type or print your full name and address and your date
of birth in the space provided on the CME Registration Form.
5. Indicate the total time spent on the activity (reading Bennie Lindeque, MD, PhD; Zach Hartman, MD, MBA;
article and completing quiz). Forms and quizzes cannot be
processed if this section is incomplete. All participants are Andriy Noshchenko, MD, PhD; Margaret Cruse, MLIS
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educational objectives
Registration Form will be separated from the quiz upon receipt at
Orthopedics. Your evaluation of this activity will in no way affect
the scoring of your quiz.
7. Send the completed form, with your $15 payment (check As a result of reading this article, physicians should be able to:
or money order in US dollars drawn on a US bank, or credit
card information) to: Orthopedics CME Quiz, PO Box 36,
Thorofare, NJ 08086, OR take the quiz online. Visit www. 1. Understand contemporary postoperative infection rates for primary total
Healio.com/EducationLab/Orthopedics for details.
hip arthroplasty (THA).
8. Your answers will be graded, and you will be advised
whether you have passed or failed. Unanswered questions will be
considered incorrect. A score of at least 80% is required to pass. 2. Understand the epidemiology of bacterial species responsible for postop-
If a passing score is achieved, Keck School of Medicine of USC
will issue an AMA PRA Category 1™ certificate within 4-6 weeks.
erative primary THA infections.
9. Be sure to mail the CME Registration Form on or before
the deadline listed. After that date, the quiz will close. CME 3. Review current interventions to decrease the primary THA infection rate.
Registration Forms received after the date listed will not be
processed. 4. Assess the volume and quality of data in the current orthopedics litera-
CME ACCREDITATION
This activity has been planned and implemented
ture regarding primary THA infections.
in accordance with the Essential Areas and policies of the
Accreditation Council for Continuing Medical Education through
the joint sponsorship of Keck School of Medicine of USC and
Orthopedics. Keck School of Medicine of USC is accredited
by the ACCME to provide continuing medical education for
physicians.
Abstract to summarize (1) the published data con-
Keck School of Medicine of USC designates this Journal- The number of primary total hip arthro- cerning the risk of surgical site infection
based CME activity for a maximum of 1 AMA PRA Category 1
Credit™. Physicians should claim only the credit commensurate plasties (THAs) performed in the United (SSI) after primary THA by type of bacteria
with the extent of their participation in the activity. States each year continues to climb, as and (2) the effect of potentially modifying
This CME activity is primarily targeted to orthopedic
surgeons, hand surgeons, head and neck surgeons, trauma does the incidence of infectious compli- factors.
surgeons, physical medicine specialists, and rheumatologists.
There is no specific background requirement for participants cations. The changing profile of antibiotic-
taking this activity. resistant bacteria has made preventing and The Cochrane Central Register of Con-
FULL DISCLOSURE POLICY
In accordance with the Accreditation Council for Continuing treating primary THA infections increas- trolled Trials, Cochrane Database of Sys-
Medical Education’s Standards for Commercial Support, all ingly complex. The goal of this review was tematic Reviews, Database of Abstracts of
CME providers are required to disclose to the activity audience
the relevant financial relationships of the planners, teachers,
and authors involved in the development of CME content. An
individual has a relevant financial relationship if he or she has
a financial relationship in any amount occurring in the last
The authors are from the Department of Orthopaedics (BL, ZH, AN), University of Colorado School of
12 months with a commercial interest whose products or Medicine; and the University of Colorado Health Sciences Library (MC), University of Colorado Health
services are discussed in the CME activity content over which Sciences Center, Aurora, Colorado.
the individual has control.
The authors have no relevant financial relationships to
The material presented in any Keck School of Medicine of USC continuing education activity does
disclose. Dr Aboulafia, CME Editor, has no relevant financial not necessarily reflect the views and opinions of Orthopedics or Keck School of Medicine of USC. Nei-
relationships to disclose. Dr D’Ambrosia, Editor-in-Chief, has ther Orthopedics nor Keck School of Medicine of USC nor the authors endorse or recommend any
no relevant financial relationships to disclose. The staff of
Orthopedics have no relevant financial relationships to disclose.
techniques, commercial products, or manufacturers. The authors may discuss the use of materials and/or
products that have not yet been approved by the US Food and Drug Administration. All readers and con-
UNLABELED AND INVESTIGATIONAL USAGE
The audience is advised that this continuing medical tinuing education participants should verify all information before treating patients or using any product.
education activity may contain references to unlabeled uses Correspondence should be addressed to: Bennie Lindeque, MD, PhD, Department of Orthopaedics,
of FDA-approved products or to products not approved by the University of Colorado, 1635 Aurora Ct, Aurora, CO 80045 (bennie.lindeque@ucdenver.edu).
FDA for use in the United States. The faculty members have
been made aware of their obligation to disclose such usage. Received: May 2, 2013; Accepted: September 30, 2013; Posted: April 15, 2014.
doi: 10.3928/01477447-20140401-08

APRIL 2014 | Volume 37• Number 4 257

n Review Article
Reviews of Effects, EMBASE, Web of Sci-
ence, and PubMed were searched. Studies
dated between 2001 and 2011 examin-
ing primary THA in adults were included.
Meta-analysis of the collected data was
performed. The pooled SSI rate was 2.5%
(95% confidence interval [Cl], 1.4%-
4.4%; P<.001; n=28,883). The pooled
deep prosthetic joint infection (PJI) rate
was 0.9% (95% Cl, 0.4%-2.2%; P<.001;
n=28,883). The pooled rate of methicil-
lin-resistant Staphylococcus aureus SSI
was 0.5% (95% Cl, 0.2%-1.5%; P<.001;
n=26,703). This is approximately 20% of
all SSI cases. The pooled rate of intraopera-
tive bacterial wound contamination was
16.9% (95% Cl, 6.6%-36.8%; P=.003;
n=2180). All these results had significant
heterogeneity. The postoperative risk of
SSI was significantly associated with in-
traoperative bacterial surgical wound con-
tamination (pooled rate ratio, 2.5; 95% Cl,
1.4%-4.6%; P=.001; n=19,049). [Ortho-
pedics. 2013; 37(4):257-265.]
T
otal hip arthroplasty (THA) has
been widely recognized as one of
the most successful orthopedic
surgeries since its introduction in the ear-
ly 1960s.1,2 Approximately 220,000 THAs
were performed in the United States an-
nually between 1998 and 2008.2 Despite
advances in surgical techniques and de-
vices, the rate of revision increased from
9/100,000 in 1990 to 15/100,000 in 2002,
with a mean revision burden of 17.5%.3
The infection burden as a proportion of
the total number of primary and revision
THAs performed increased from 0.66% in
1990 to 2.18% in 2009.4,5 The estimated
nationwide total hospital cost for treat-
ment of hip PJI was approximately $200
million in 2009.4
There are 3 main types of postoperative
surgical site infection (SSI) after THA: (1)
acute postoperative (early onset), appearing
within 3 months postoperatively; (2) de-
layed deep, appearing 3 to 12 months post-
operatively; and (3) late hematogenous, ap-
pearing more than 1 year postoperatively.1
258
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Description of Intervention
Ultra-clean-air systems, limiting the
number of personnel in the operating
room, improved barrier draping, and the
use of sterile suction systems reduced the
risk of exogenous wound contamination,
decreasing the infection rate from 7% to
10% in the 1960s to 1.5% to 3% in the
1990s.1,6 Bacteriological tests suggested
that skin-concomitant bacteria, in particu-
lar Staphylococcus aureus, were the most
typical isolates in cases of both early and
late infection.6 Bacteriologic analysis of
swabs taken from surgical wounds at the
end of surgery showed that 15% of surgical
wounds were contaminated by skin flora.7
Preoperative application of an iodophor
plastic adhesive drape decreased the risk of
perioperative bacterial wound contamina-
tion to 1.6%.7 The association of postoper-
ative infection with intraoperative bacterial
wound contamination was not evaluated.
However, it was shown in the 1980s that
a combination of aseptic measures, such
as ultra-clean-air systems with periop-
erative antibiotic prophylaxis, decreased
the postoperative infection rate to 0.6%.8
Meta-analysis showed that the rate of deep
infection after THA varied from 1.2% to
2.3% and was lower if antibiotic-loaded ce-
ment was used.9 A Cochrane review dem-
onstrated that application of closed suction
surgical wound drainage did not decrease
the risk of SSI after THA.10
The most significant risk factors of SSI
and PJI can be classified into 3 groups: (1)
preoperative: prior rheumatoid or septic
arthritis (odds ratio [OR]=2.2), other prior
infectious diseases (OR=1.8-2.3), malig-
nancy (OR=2.4), prior THA (OR=2.2),11
or nasal carrier of S aureus (relative
risk=8.9)12; (2) perioperative: contaminat-
ed wound (OR=4.3)13; and (3) postopera-
tive: SSI (OR=27.5), wound dehiscence
(OR=21.5), or hematoma (OR=2.7).11
The risk of PJI was associated with intra-
operative surgical wound contamination
by skin-concomitant bacteria (OR=2.1);
however, this finding was not statistically
significant due to the small number of
cases with intraoperative surgical wound
contamination.14
How the Intervention Might Work
Studies from the early 2000s showed
that strains of methicillin-resistant S au-
reus (MRSA), which had previously been
observed in hospitals and patients with
chronic diseases, were emerging in the
community and in an increasing number
of healthy carriers.15,16
Currently, cefazolin and cefuroxime
are recommended for patients undergoing
orthopedic procedures, and clindamycin
or vancomycin is recommended for pa-
tients with known MRSA colonization.17
However, pre- or perioperative admin-
istration of cefazolin and methicillin did
not decrease the risk of PJI significantly.11
Preoperative selective decolonization by
intranasal administration of mupirocin
and chlorhexidine baths decreased the
risk of postoperative infection to 1.2%18;
however, 27% of MRSA isolates causing
hip and knee PJI were resistant to mupi-
rocin.19 Use of at-home chlorhexidine
decreased the risk of deep infection after
THA; however, this effect was not sig-
nificant due to the low rate of infectious
cases.20,21 A Cochrane review with meta-
analysis revealed no significant decrease
in postoperative SSI associated with hair
removal, regardless of method.22
The use of ultra-clean laminar airflow
ventilation systems was associated with a
higher rate of SSI after THA (OR=1.71).23
This may suggest that in contemporary op-
erating rooms, skin-concomitant bacteria
determine intraoperative surgical wound
contamination and risk of postoperative
SSI/PJI rather than exogenous infection.
Why This Review Is Important
The change in proportion of antibiotic-
resistant surgical wound pathogens in-
fluences THA infection prophylaxis and
treatment. Thus, assessment of postop-
erative infection rate, taking into consid-
eration pathogenic microorganisms such
as MRSA and other methicillin-resistant
ORTHOPEDICS | Healio.com/Orthopedics

microorganisms, is an important task. Tak-
ing into consideration contemporary rates
of postoperative SSI (approximately 2.5%)
and PJI (approximately 1%) after primary
THA and that rates of different microorgan-
isms varied from 40% to 60% (S aureus)
to 1% (Propionibacterium species), more
than 4200 cases of primary THA should be
included in the analysis to obtain statisti-
cally significant results with 95% statisti-
cal power. To obtain statistically significant
results concerning the association between
intraoperative bacterial surgical wound
contamination and postoperative infection,
125 cases or more of intraoperative wound
contamination and a corresponding number
of uncontaminated cases should be ana-
lyzed. It is difficult to collect this number
of cases in 1 study, so pooling data with a
meta-analysis offers a solution. Moreover,
pooling data from different independent
studies provides more representative results
than data obtained from a single study.
Materials and Methods
Objectives
This review assessed the risk of SSI af-
ter primary THA while taking into consid-
eration the type of complication; the bac-
terial types, including methicillin-resistant
strains; the effect of potentially modifying
factors; and the heterogeneity of the re-
sults obtained by different studies.
Inclusion Criteria
Randomized controlled trials; prospec-
tive cohort studies; case series; and retro-
spective comparative and noncomparative
studies with a follow-up greater than 2
months focusing on the evaluation of post-
operative SSI and intraoperative surgical
wound contamination by type of bacteria
were sought. Participants were skeletally
mature adults (male and female) 18 years
and older undergoing primary THA.
Outcome Measures
Primary outcomes included:
1. Rate of postoperative SSI by type of
bacteria, including MRSA
APRIL 2014 | Volume 37• Number 4
cme
ARTICLE
2. Rate of postoperative deep PJI by
type of bacteria, including MRSA
3. Rate of intraoperative bacterial surgi-
cal wound contamination by type of bacte-
ria, including MRSA
4. Association of postoperative SSI with
intraoperative bacterial surgical wound
contamination
Secondary outcomes included:
1. Perioperative antibiotic prophylaxis
(yes/no/nonspecified)
2. Air-cleaning system in the operating
room (yes/no/nonspecified)
3. Type of implantation (cemented/non-
cemented/nonspecified)
4. Postoperative follow-up (less than 12
months/12 months or more/nonspecified)
Search Methods
The following databases were
searched: Cochrane Central Register
of Controlled Trials (CENTRAL), Co-
chrane Database of Systematic Reviews
(CDSR), Database of Abstracts of Re-
views of Effects (DARE), EMBASE,
Web of Science, and PubMed. The search
strategy was developed in Ovid Medline
and translated to PubMed, EMBASE,
Web of Science, CENTRAL, CDSR, and
DARE. Medline, Embase, and Web of
Science strategies are shown in Appen-
dix A (available at the end of the PDF
of this article). A sensitive search was
performed to identify as many relevant
trials as possible. Only studies published
between 2001 and 2011 were included.
No language limits were applied. The
search was performed by a University of
Colorado Health Sciences Library Pro-
fessional Research Librarian.
Reference lists of review articles, in par-
ticular Cochrane systematic reviews, were
also reviewed to identify eligible studies.
Data Collection, Analysis, Extraction,
and Management
One reviewer (Z.H.) screened the ti-
tles, abstracts, and, when necessary, full
texts to determine potentially eligible
studies. Full-text reports of selected stud-
n Review Article
ies were then analyzed by 2 reviewers
(A.N., Z.H.). Disagreements regarding
inclusion were resolved by discussion.
Excluded studies were listed with reason
for exclusion.
Data were extracted from the included
studies by 1 reviewer (A.N.) and checked
by another (B.L.). The following data
were collected: (1) general information:
authors, title, publication status, year of
publication, country, study design, spon-
sorship, and study objectives; (2) partici-
pants: inclusion and exclusion criteria,
number in intervention groups, ages,
sexes, baseline comparability, dropouts;
(3) trial characteristics: design, length
of follow-up, randomization, allocation
concealment, and blinding of assessors
if applicable; (4) interventions: cemented
or noncemented, perioperative antibi-
otic prophylaxis, preoperative skin treat-
ment, air-cleaning system in the operat-
ing room, and postoperative follow-up
period; and (5) intra- and postoperative
outcomes.
Only groups within a study that used
the same surgical technique and device
were included in the analysis.
Studies with a dropout rate of more
than 30% at 24-month follow-up were ex-
cluded.
Assessment of Risk of Bias
The risk of bias for each study included
in the review was defined independently
by 2 reviewers (A.N., Z.H.) using Cow-
ley’s score.24 The items were scored with
yes or no. Studies were selected for analy-
sis if at least 6 of the 16 criteria were met,
and risk of bias was defined using Review
Manager 5.1 (The Nordic Cochrane Cen-
ter, Copenhagen, Denmark). Agreement
between the 2 independent assessments
was defined by kappa test. Disagreements
were resolved by discussion.
Measures of Studied Effects
The studied effects were binary data
and were assessed as a ratio of studied
evidence to sample size at follow-up. An
259
n Review Article
Figure 1: Flow chart of study inclusion in the meta-analysis.
inverse-variance method was used for
combining data across studies. Pooled
rates with 95% confidence intervals
(CIs) were calculated. To evaluate the
influence of modifying factors, grouping
analysis was applied. A random-effects
model was used for pooling data in each
group.
Assessment of Heterogeneity
Statistical heterogeneity of pooled
data was defined by chi-square test
(P<.05 represented heterogeneity) and
I2 test with the following interpretation
260
cme
ARTICLE
of heterogeneity: less than 30%=low;
30% to 60%=moderate; greater than
60%=high.
Assessment of Publication Bias
Funnel plots were used to evaluate the
risk of publication bias.
Data Synthesis
A meta-analysis of studied effects was
performed by defining pooled rates in
each group of interest with 95% CIs. To
summarize data, a random-effects model
was applied. The GRADE approach was
applied to evaluate the quality of the re-
vealed evidence.25,26
Sensitivity Analysis
Sensitivity analysis was performed by
extracting studies that showed results sig-
nificantly different from the pooled result.
Results
Description of Studies
Electronic searches provided a total
of 1024 citations, and 67 were identified
from other sources. After adjusting for du-
plicates, 918 remained and were screened.
Of these, 904 were discarded because
they did not meet the study criteria. The
remaining 14 citations were examined in
more detail. A further 6 studies did not
meet all of the inclusion criteria, leaving 8
studies that were included in the system-
atic review and meta-analysis (Figure 1).
Included Studies
Eight studies selected for the review
were published as full-text articles in
English and were conducted in the fol-
lowing countries: United States,27 Can-
ada,28 United Kingdom,29 Ireland,30,31
Greece,32 Hong Kong,33 and Poland34
(Table A, available at the end of the PDF
of this article). Six studies were prospec-
tive, including 5 case series,28,30-32,34 1
was a nonrandomized cohort study,29 and
2 were retrospective case series.27,33 The
search revealed no randomized controlled
clinical trials meeting the inclusion crite-
ria. The postoperative follow-up period
ranged from 2 to 120 months. Dropout
was reported by 6 studies and did not ex-
ceed 20%.27-31,33
The included studies involved 28,883
participants after THA, including 23,729
primary THAs,27,29-31,33 2587 revision
THAs,29,31,33 and 2567 combined pri-
mary and revision THAs.28,32 Mean age
in the study groups was reported by 6
studies27,29,32-34 and ranged from 40 to
72 years (Table A, available at the end of
the PDF of this article). The male:female
ratio was reported by 5 studies27,29,31-33
ORTHOPEDICS | Healio.com/Orthopedics

and ranged from 0:5 to 0:7. Two studies
reported results of cemented THAs,28,30
1 study reported results of uncemented
THAs,27 3 studies reported results of com-
bined (cemented, uncemented, or hybrid)
THAs,29,31,33 and 2 studies did not specify
the type of implant fixation.32,34 Preopera-
tive infection status of enrolled patients
was reported in 3 studies.31-33 Antibiotic
prophylaxis was reported by 7 studies
(Table B, available at the end of the PDF
of this article).27,28,30-34 Antibiotic prophy-
laxis was applied as a standard procedure
for all patients in 5 studies,27,30-32,34 was
partially used in 2 studies,28,33 and was not
specified in 1 study.29 Preoperative wound
site preparation was reported in 3 studies
(Table B, available at the end of the PDF
of this article).27,30,31 Seven studies re-
ported testing of surgical wound bacterial
contamination.27-33 All studies reported
data concerning postoperative infection,
including deep PJI. Five studies reported
that an air-cleaning system was used in
the operating room during THA.27,28,30-32
Three studies did not specify this.29,33,34
Risk of Bias in Included Studies
The 2 independent bias evaluations
demonstrated good agreement (kappa
coefficient, 0.95; standard error, 0.027;
P=.56). All studies were nonrandomized,
including 7 case series27,28, 30-34 and 1 co-
hort study.29 None of the studies reported
the type of hip prosthesis. Three studies
did not report the number of enrolled men
and women.28,30,32 Seven studies did not
report preoperative diagnosis.27-31,33,34
Only 2 studies reported patient weight
and body mass index.27,29 This suggests a
risk of selection bias in all included stud-
ies (Figure 2). A high risk of performance
bias was found for all 8 studies. This bias
is attributed to the fact that personnel and
participants could not be blinded to the
type of complications associated with
infection. Only 1 study reported that the
evaluation of clinical and radiologic out-
comes, including statistical analysis, was
independent of operating surgeon.34 This
APRIL 2014 | Volume 37• Number 4
n Review Article
cme
ARTICLE
suggests a high risk of detection bias in
the other 7 studies (Figure 2).27-33 Two
studies did not report the number of pa-
tients lost to follow-up, leaving them vul-
nerable to attrition bias.32,34
In summary, 100% of included studies
were at risk of selection and performance
bias, 87.5% were at risk of detection bias,
and 25% were at risk of attrition bias (Fig-
ure 3).
Primary Outcomes
Rate of Postoperative Surgical Site In-
fection. In the 8 included studies, the rate
of postoperative SSI ranged from 0.3%
to 63.6%. The pooled SSI rate was 2.5%
(95% CI, 1.4%-4.4%; P<.001; n=28,883;
high heterogeneity: I2=95.7%; P<.001).
Rate of Postoperative Deep Prosthetic
Joint Infection. In the 8 included studies,
the rate of postoperative deep PJI ranged
from 0.1% to 11.1%. The pooled deep
Figure 2: Review authors’ judgments about each
PJI rate was 0.9% (95% CI, 0.4%-2.2%; risk of bias item for each included study.
P<.001; n=28,883; high heterogeneity:
I2=94.4%; P<.001). This is approximately
36% of all SSI cases. was cultured in 6 studies, with rates rang-
Rate of Bacteria Types Associated With ing from 0% to 13.6%.27-29,32-34 The pooled
Surgical Site Infection. Staphylococcus rate was 0.5% (95% CI, 0.2%-1.3%;
aureus was found to be a cause of SSI in P<.001; n=26,505; high heterogeneity:
6 studies.27-29,31,33,34 Rates of SSI with iso- I2=88.9%; P<.001). This is approximately
lated S aureus ranged from 0.2% to 27.3%. 20% of all SSI cases. Streptococci were
The pooled rate of SSI with S aureus reported in 2 studies, with a pooled rate
was 1.3% (95% CI, 0.6%-2.5%; P<.001; of 0.2% (95% CI, 0.1%-0.3%; P<.001;
n=28,185; high heterogeneity: I2=95.3%; n=20,834; low heterogeneity: I2=0%;
P<.001). This is approximately 52% of P=.784).28,29 This is approximately 8% of
all SSI cases. Staphylococcus epidermidis all SSI cases. Gram-negative bacilli were
Figure 3: Review authors’ judgments about each risk of bias item presented as percentages across all
included studies.
261
n Review Article
reported by 2 studies, with rates of 0.04%29
and 1%.34 The pooled rate was 0.2% (95%
CI, 0%-4.6%; P<.001; n=16,770; high het-
erogeneity: I2=96.3%; P<.001). This is ap-
proximately 8% of all SSI cases.
Other and mixed bacteria isolates, in-
cluding Escherichia coli, Klebsiella pneu-
moniae, Pseudomonas aeruginosa, Pro-
teus mirabilis, and others, were reported
by 5 studies, with rates ranging from
0.04% to 4.5%.27-29,32,33 The pooled rate
was 0.4% (95% CI, 0.2%-1.0%; P<.001;
n=26,026; high heterogeneity: I2=85.8%;
P<.001). This is approximately 16% of all
SSI cases.
Rate of Methicillin-resistant Bacteria
Associated With Postoperative Surgical
Site Infection. Antibiotic-resistant bacteria
reported included MRSA and methicillin-
resistant S epidermidis (MRSE). Methi-
cillin-resistant S aureus was reported by
5 studies, with rates varying from 0.1% to
1.9%.27,29,31,33,34 The pooled rate was 0.5%
(95% CI, 0.2%-1.5%; P<.001; n=26,703;
high heterogeneity: I2=95.7%; P<.001).
This is approximately 20% of all SSI cas-
es. Methicillin-resistant S epidermidis was
cultured in 1 study, with a rate of 0.1%
(95% CI, 0%-0.2%; P<.001; n=5060).27
Rate of Intraoperative Bacterial Surgi-
cal Wound Contamination. Four studies
reported cases of intraoperative surgical
wound bacterial contamination, with rates
ranging from 2.7% to 59%.28,30,32,33 The
pooled rate was 16.9% (95% CI, 6.6%-
36.8%; P=.003; n=2180; high heteroge-
neity: I2=92.8%; P<.001).
Rate of Bacteria Types Associated With
Intraoperative Surgical Wound Contami-
nation. Three studies reported that S au-
reus was cultured from swabs taken from
the surgical wound, with rates ranging
from 0.5% to 27.3%.28,32,33 The pooled rate
was 3.5% (95% CI, 0.2%-36.5%; P=.019;
n=2125; high heterogeneity: I2=96.5%;
P<.001). Four studies reported S epider-
midis, with rates ranging from 0.3% to
18.2%.28,30,32,33 The pooled rate was 3.5%
(95% CI, 0.3%-27.3%; P=.005; n=2180;
high heterogeneity: I2=95.6%; P<.001).
262
cme
ARTICLE
Streptococci were reported by 2 stud-
ies, including Streptococcus pyogenes,
Streptococcus viridans, and Streptococ-
cus salvarius, with rates of 0.3%28 and
1.8%.30 The pooled rate was 0.6% (95%
CI, 0.1%-3.6%; P<.001; n=2048; high
heterogeneity: I2=69.4; P=.071). Esche-
richia coli was reported in 3 studies, with
rates ranging from 0.1% to 13.6%.28,32,33
The pooled rate was 1.1% (95% CI, 0%-
23.5%; P=.008; n=2125; high heterogene-
ity: I2=93.8; P<.001). Gram-negative ba-
cilli were reported in 1 study, with a rate
of 1.8% (95% CI, 0.3%-11.8%; P<.001;
n=55).30 Other bacteria and mixed bacteri-
al wound contamination were reported in
4 studies, with rates ranging from 0.4% to
4.6%.28,30,32,33 The pooled rate was 1.6%
(95% CI, 0.4%-5.9%; P<.001; n=2180;
high heterogeneity: I2=76.5%; P<.001).
Rate of Methicillin-resistant Bacteria
Associated With Intraoperative Surgical
Wound Contamination. One study report-
ed cases of MRSA isolated from surgical
wounds during THA revisions caused by
PJI, with a rate of 46.2% (95% CI, 22.4%-
71.9%; P=.782; n=13).33 However, this
finding is not significant due to the small
number of cases.
Association of Postoperative Surgical
Site Infection With Intraoperative Sur-
gical Wound Bacterial Contamination.
Five studies reported cases of postopera-
tive SSI in patients with clean intraopera-
tive surgical wounds and in patients with
bacterial contamination of their surgical
wounds.29,30,32-34 These results allowed
evaluation of postoperative SSI risk asso-
ciated with intraoperative bacterial surgi-
cal wound contamination. Pooled risk ra-
tio was 2.5 (95% CI, 1.4%-4.6%; P=.001;
n=19,049; low heterogeneity: I2=0%;
P=.685) (Figure A, available at the end
of the PDF of this article),27,28,30-34 sug-
gesting a significant association between
intraoperative surgical wound bacterial
contamination and risk of postoperative
SSI. The pooled data were insufficient to
assess the contribution of bacterial types
in relation to the risk of SSI and PJI.
Secondary Outcomes
Perioperative Antibiotic Prophylaxis.
Perioperative antibiotic prophylaxis was
given to all patients in 2 studies, with a
pooled risk of SSI of 1% (95% CI, 0.7%-
1.6%; P<.001; n=1845; low heterogene-
ity: I2=0%; P<.562).30,31 Three studies
showed a risk of SSI after partially used
(not in all patients) perioperative antibi-
otic prophylaxis for primary THA, with a
pooled SSI risk of 1.4% (95% CI, 0.5%-
4.4%; P<.001; n=21,884; high hetero-
geneity: I2=97.1%; P<.001).27,29,33 This
difference is not significant, but higher
heterogeneity in the second group sug-
gests that nonregular use of perioperative
antibiotic prophylaxis may lead to less
certain outcomes after primary THA.
Air-cleaning System in the Operating
Room. Three studies reported that air-
cleaning systems were used in the operat-
ing room during primary THA, with rates
of SSI ranging from 0.3% to 1.8%.27,30,31
The pooled risk of SSI was 0.7% (95%
CI, 0.2%-1.9%; P<.001; n=6905; high
heterogeneity: I2=85.3%; P=.001). Use of
an air-cleaning system was not specified
in 2 studies, with SSI rates of 2.2%29 and
4.4%33 and a pooled rate of 2.9% (95%
CI, 1.6%-5.3%; P<.001; n=16,824; high
heterogeneity: I2=87.6%; P=.005). This is
significantly (P=.018) higher than in stud-
ies using air-cleaning systems.
Type of Implantation (Cemented/Non-
cemented). Primary cemented THA was
performed in 1 study, with a risk of SSI
of 1.8% (95% CI, 0.3%-11.8%; P<.001;
n=55).30 Primary noncemented THA was
performed in 1 study, with a risk of SSI
of 0.3% (95% CI, 0.2%-0.5%; P<.001;
n=5060).27 This difference is not statisti-
cally significant.
Postoperative Follow-up. Two stud-
ies had less than 12 months of follow-up,
with a pooled risk of SSI of 2.7% (95%
CI, 1.8%-4.1%; P<.001; n=19,320; high
heterogeneity: I2=90.2%; P<.001).29,34
Twelve or more months of postopera-
tive follow-up was reported in 6 stud-
ies.27,28,30-33 The pooled risk of SSI was
ORTHOPEDICS | Healio.com/Orthopedics

3.8% (95% CI, 1.9%-4.1%; P<.001;
n=9578; high heterogeneity: I2=97.1%;
P<.001). The difference between these 2
groups was not significant.
Deep PJI with less than 12 months of
postoperative follow-up was reported in 2
studies, with a pooled risk of 0.3% (95%
CI, 0.1%-0.9%; P<.001; n=19,320; high
heterogeneity: I2=84.6%; P<.001).29,34
Six studies reported 12 or more months
of postoperative follow-up, with a pooled
risk of deep PJI of 1.4% (95% CI, 0.5%-
3.7%; P<.001; n=9578; high heteroge-
neity: I2=91.6%; P<.001).27,28,30-33 The
difference was statistically significant
(P=.037), suggesting that more than 12
months of follow-up revealed a higher
rate of deep PJI than did fewer than 12
months of follow-up.
Discussion
Summary of Main Results
Eight nonrandomized clinical studies
(7 case series and 1 cohort study) involv-
ing 28,883 participants were included to
assess the risk of SSI after THA. Informa-
tion concerning sponsorship of these pub-
lications was not provided.
All studies reported rate and number
of SSIs after THA, with a pooled rate of
2.5% (95% CI, 1.4%-4.4%; P<.001). De-
spite statistical significance of the pooled
result, the level of evidence is low due to
the serious limitations in the design of the
studies, high risk of bias, and high hetero-
geneity of the combined data.
Deep PJI was also reported by all in-
cluded studies, with a pooled rate of 0.9%
(95% CI, 0.4%-2.2%; P<.001). Despite
statistical significance, the level of this evi-
dence is also low, due to the same problems.
Pooling data concerning bacteria cul-
tured in SSI cases demonstrated the preva-
lence of skin concomitants such as S aure-
us (1.3%; 95% CI, 0.6%-2.5%),27-29,31,33,34
and S epidermidis (0.5%; 95% CI, 0.2%-
1.3%), reported by 6 studies.27-29,32-34
In addition, 5 studies revealed the fol-
lowing species sometimes found in com-
bination with S aureus and S epidermidis:
APRIL 2014 | Volume 37• Number 4
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ARTICLE
E coli, K pneumoniae, P aeruginosa, P
mirabilis, and others, with a pooled rate
of 0.4% (95% CI, 0.2%-1.0%).27-29,32,33
Streptococci28,29 and gram-negative ba-
cilli29,34 were reported by 2 studies, with
a pooled rate of 0.2%. The most common
antibiotic-resistant strain was MRSA, re-
ported by 5 studies and with a pooled rate
of 0.5% (95% CI, 0.2%-1.5%).27,29,31,33,34
One study cultured MRSE in 0.1% (95%
CI, 0%-0.2%) of cases.27 All of these re-
sults are statistically significant, but the
level of evidence is low due to the meth-
odological limitations of the studies, high
heterogeneity of the results, and small
number of studies reporting several find-
ings.
Intraoperative bacterial wound con-
tamination was reported by 4 studies, with
a pooled rate of 16.9% (95% CI, 6.6%-
36.8%).28,30,32,33 Despite statistical sig-
nificance (P=.003), the level of evidence
is low due to the methodological limita-
tions of the studies and high heterogene-
ity of the results. Skin concomitants were
the most typical isolates from the surgical
wound, including S aureus (3.5%; 95% CI,
0.2%-36.5%),28,33 S epidermidis (3.5%;
95% CI, 0.3%-27.3%),28,30,32,33 strepto-
cocci (0.6%; 95% CI, 0.1%-3.6%),28,30
and gram-negative bacilli (1.8%; 95% CI,
0.3%-11.8%).30 E coli and other bacteria
were reported with pooled rates of 1.1%
(95% CI, 0%-23.5%) and 1.6% (95% CI,
0.4%-5.9%), respectively.28,32,33 Pooled
data concerning bacterial contamination
of the surgical wound are statistically sig-
nificant, but the level of evidence is low
due to high heterogeneity, methodological
limitations, and a small number of studies
reporting several results.
Combining the results of 5 stud-
ies showed that intraoperative bacterial
wound contamination resulted in a more
than 2-fold increased risk of SSI after
THA (Figure A, available at the end of
the PDF of this article).29,30,32-34 This re-
sult was statistically significant with low
heterogeneity, suggesting that the results
of different studies were relatively consis-
n Review Article
tent. However, the level of evidence is low
because of methodological limitations of
the studies and a high risk of bias.
Collected data and pooled results do
not allow a conclusion concerning effica-
cy of antibiotic prophylaxis, air-cleaning
systems in the operating room, and type of
implantation (cemented or noncemented)
for prevention of SSI and PJI after THA.
Duration of follow-up less than 12
months after primary THA can signifi-
cantly underestimate the risk of PJI. De-
spite the statistical significance of this
finding, the level of evidence is low.
Overall Completeness and Applicability
of Evidence
The included studies provide the most
complete information available concern-
ing rates of SSI and deep PJI after prima-
ry THA; however, methods of diagnosis
were different, adding heterogeneity to the
pooled results. Information concerning
bacteriologic analysis of SSI and surgical
wound swab isolates was presented par-
tially. Rates of SSI associated with MRSA
were presented partially. Information con-
cerning surgical wound intraoperative
bacterial contamination—in particular
by MRSA and other antibiotic-resistant
strains—and its association with post-
operative SSI and PJI was limited. Data
concerning potential confounding factors,
such as preoperative diagnosis, type of hip
prosthesis, type of prosthesis fixation, use
of antibiotic-loaded cement, preoperative
skin treatment, antibiotic prophylaxis, and
air-cleaning system in the operating room,
were incomplete.
Quality of the Evidence
The overall quality of included studies
is poor. All are nonrandomized observa-
tional studies with serious limitations.
Overall sample size allows obtaining
several statistically significant results.
However, the level of evidence of these
findings is low or very low due to hetero-
geneity of the pooled data and the risk of
bias caused by the studies’ design.
263
n Review Article
Potential Biases in the Review Process
The review was conducted following
contemporary requirements for system-
atic reviews and meta-analysis of studies
that evaluate health care interventions.35-37
Comprehensive searches were performed
to identify relevant studies. Unfortunately,
no randomized controlled clinical trials met
the inclusion criteria. Therefore, the au-
thors had to include nonrandomized stud-
ies while taking into consideration the risk
of corresponding biases.36,37 The results of
the meta-analysis are limited by the qual-
ity of the studies identified in the review.
Theoretically, studies relevant to the review
may have been missed by the search. How-
ever, the authors’ analysis demonstrated
that this potential loss would not change
the results significantly. This review was
conducted independent of industry.
Agreement and Disagreement With
Other Studies or Reviews
Pooled data concerning postopera-
tive SSI after primary THA obtained in
this study were similar to previously pub-
lished results. A 2008 Cochrane review
summarized outcomes of 12 randomized
or quasi-randomized clinical trials study-
ing risk of postoperative infection after
THA in 1415 participants.10,38-49 Rates of
postoperative infection varied from 0% to
32%. The pooled rate was 3.6% (95% CI,
1.8%-7.4%). This is slightly higher than
that of the current study, but the differ-
ence is not statistically significant. Another
review summarized data of 6 randomized
or quasi-randomized clinical trials exam-
ining the risk of deep PJI after primary
cemented (with or without antibiotics)
THA in 15,137 hips.9 Studies included in
that review were published between 1987
and 1997. Rates of postoperative infec-
tion varied from 0.4% to 8.6%. The pooled
rate of deep infection was 1.5% (95% CI,
0.7%-3.0%). This is slightly higher than
the pooled rate obtained in the current re-
view, but the difference is not significant.
The current authors found no reviews that
met their inclusion criteria summarizing
264
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ARTICLE
data concerning the risk of SSI and/or PJI
associated with different bacterial species,
in particular antibiotic-resistant strains.
Since the 1970s, it has been well-known
that skin flora are the most common isolate
from surgical wounds and postoperative
infections.6,7,50 Data concerning the as-
sociation between intraoperative surgical
wound bacterial contamination and the risk
of postoperative infection after THA were
published but did not reach statistical sig-
nificance due to the relatively small num-
ber of cases.14 The current review showed a
statistically significant association by pool-
ing data from different studies.
Data concerning the appearance of
methicillin-resistant strains of S aureus and
other bacteria in SSI and PJI after THA have
been published during the past decade.17
Risks associated with methicillin-resistant
infection are likely high but not well evalu-
ated, which is shown in the current review.
No significant disagreements with previ-
ously published data were revealed.
Conclusion
This study clarifies primary THA in-
fection rates by type of bacteria, shows an
increased risk of SSI given positive intra-
operative cultures, and establishes a need
for future research.
During the past decade, the most sig-
nificant likelihood of SSI rate after pri-
mary THA was approximately 2.5% (95%
CI, 1.4%-4.4%), and the most significant
likelihood rate of deep PJI after primary
THA was approximately 0.9% (95% CI,
0.4%-2.2%). Skin flora is the most typical
isolate in cases of postoperative infection.
Approximately 20% of SSIs are associ-
ated with methicillin-resistant strains.
In current clinical conditions, the risk
of intraoperative bacterial wound contam-
ination is approximately 16.9% (95% CI,
6.6%-36.8%). The skin flora determines
the risk of intraoperative wound contami-
nation, increasing the risk of postoperative
infection after THA approximately 2-fold
despite contemporary measures of aseptic
and antiseptic prophylaxis.
This review highlights the paucity of
high-quality studies on the risk of compli-
cations associated with type of bacteria,
especially methicillin-resistant infections
after THA. Well-designed randomized,
controlled trials and economic studies are
needed to assess the clinical effectiveness
and cost-effectiveness of methods to de-
crease infection and risk of reoperation
after primary THA.
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Appendix A Search Strategies and Strings

Medline strategy + first 100 results:

• .mp = keyword in any field

• .tw = title words
• $ = truncation device (right end “catch all”)
• .fs = “floating subheading” (not used yet, although it might be incorporated later)
• #36 is larger set bcs it includes the broad terms, postoperative complication$ and all
prosthesis related infections (not just bacterial ones)
• #38 is the set without those 2 terms (much more focused on your question)
28 exp treatment outcome/ 465066
29 therapy.fs. 1201998
30 complications.fs. 1360604

31 mortality.fs . 332769
32 (revision and (bone or joint or hip or knee or ankle or wrist or knuckle or 9877
shoulder or prostheS)) .tw.
33 1 or 2 or 3 or 4 or 5 or 6 68866
34 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 371642
35 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 1302560
36 33 and 34 and 35 3209
37 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 342005
38 33 and 35 and 37 970
 Table A Characteristics of the selected studies
Study Study No Mean Gender Initial Implantation Preo- Perioperative Assessment of Monitoring of Bacterio- Follow- Air Cowley’s
design age selection perative antibiotic perioperative postoperative logic up, cleaning
(Country) m/f (primary/ (cemented/ infection prophylaxis bacterial wound infectious month system in score
ratio revision) other) contamination complications analysis of operation
postoperative room
infection
Byrne 2007 no compli-
(Ireland) pCS 55 ns ns primary cemented ns yes yes yes 49.6±3.2 yes 7
cations
Hamilton 2008 primary&
(Canada) pCS 1993 ns ns cemented ns yes/no yes yes yes 6-120 yes 10
revision
Petsatodis
64.3 primary& no compli-
2009 (Greece) pCS 110 0.6 ns yes yes yes yes 12-48 yes 6
revision cations
(25-81)
Ip 2005
70 cemented,
(Hong Kong)
22 0.5 revision cementless, yes yes yes yes ns 13-98
rCS (54-82) hybrid ns 7

533 ns ns primary ns ns ns ns ns ns ns
Wójkowska-
March 2008 pCS 479 20-80 0.7 ns ns ns yes no yes yes 2 ns 8
(Poland)
Ridgeway
pCS cemented/
2005 (UK) 16291 50-85 0.6 primary ns yes/no yes yes yes 3 ns 10
cementless
cemented/
2550 50-85 0.6 revision ns yes/no yes yes yes 3 ns
cementless
Pulido 2009
62 43
(USA) rCS 5060 0.7 primary uncemented ns yes yes yes yes yes 9
(15-94) 12-76
Walls 2008
cemented,
(Ireland) 72.7
pCS 1790 ns primary cementless, yes yes yes yes yes 9-88 yes 10
(53-81)
hybrid
Note: pCS – prospective case series or cohort study, rCS – retrospective case series or cohort study
Table B Preoperative wound site preparation and antibiotic prophylaxis
Study Preoperative wound site preparation Antibiotic prophylaxis Application

Byrne 2007 Chlorhexidine shower on the morning of Cefuroxime (1.5 g) intravenously every 8 Standard protocol
surgery hours postoperatively for 24 hours

Cephamadol (2.0 g) intravenously during Partially used

Hamilton 2008 Not specified
surgery and 1 g after surgery
Petsatodis 2009 Alcohol solution of povidone-iodine (1%) Cefuroxime (1.5 g) before skin incision and Standard protocol
every 8 hours for 48 hours
Ip 2005 Not specified Intravenous antibiotics for 6 weeks between Revision
the 2 stages of reconstruction
Vancomycin loaded cement (2 g) Revision in
patients with
Tabromicine (1g/ 40 g of cement powder)
positive MRSA
culture
Wójkowska- Not specified Perioperative administration of Standard protocol
March 2008 cephalosporines (five 1 g doses)
Ridgeway 2005 Not specified Not specified -

Pulido 2009 Alcohol and iodine lavage plus an Incise Perioperative administration of antibiotics Standard protocol
adhesive drape for 24 hours
Walls 2008 Not specified Cefuroxime (1.5 g) three doses during and Standard protocol
after surgery for 16 hours

Note: MRSA - Methicillin- resistant Staphylococcus aureus

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