Antibiotic Powder for SSI Prevention in Extremity Surgery

Research Article
Intrasite Antibiotic Powder for the
Prevention of Surgical Site
Infection in Extremity Surgery: A
Systematic Review
Abstract
Introduction: Although the role of intrasite antibiotic powder in
preventing surgical site infections (SSIs) has been extensively
explored in spinal surgery, it remains underevaluated in the other
orthopaedic subspecialties. This systematic review examines the
utilization of intrawound antibiotic powder as a prophylactic measure
against SSIs in orthopaedic procedures.
Methods: Following the Preferred Reporting Items for Systematic
Reviews and Meta-Analyses guidelines, electronic searches were
conducted on Ovid MEDLINE, and PubMed. Only English language,
nonspine clinical studies published before May 2018 were included.
Results: The initial search identified 179 individual citations, and 11
studies met the eligibility criteria. All included studies were level III
retrospective studies. Represented subspecialties included total joint
arthroplasty, upper extremity, foot and ankle, and trauma. Eight
studies demonstrated a statistically significant decrease in SSIs with
the use of intrasite antibiotic powder.
Discussion: There are no current guidelines for the use of intrasite
antibiotic powder for the prevention of SSIs in orthopaedic
procedures. Despite the lack of high-quality evidence available in the
literature, published smaller studies do suggest a significant protective
effect. However, recommendations with regard to this technique after
common orthopaedic procedures cannot yet be made.
Surgical site infections (SSIs) re-
main a persistent clinical issue,
accounting for 22% of healthcare-
related infections.
1
These infections
place a significant burden on health-
care systems, costing 1 to 10 billion
dollars annually.
2
Many studies have
documented the significant morbidity,
both short term and long term, for
patients affected by SSIs after an
orthopaedic procedure.
3–5
Postop-
erative management is often compli-
cated by multiple revision surgeries,
prolonged antibiotic therapy, and
extended hospitalizations, which
consequently negatively influences
patient-reported outcomes and in-
creases healthcare cost. Typically, a
first-generation cephalosporin or
clindamycin has been the benchmark
for prophylactic antibiotic therapy
for orthopaedic and extremity pro-
cedures. These antibiotics are dosed
within 1 hour of the surgical incision
and in some instances continued 24
hours postoperatively.
6,7
These an-
tibiotics not only cover Staphylo-
coccus aureus, the most common
single organism in extremity SSIs,
but also offer broad coverage for
Stephen D. Fernicola, MD
Michael J. Elsenbeck, MD
Patrick D. Grimm, MD
Alfred J. Pisano, MD
Scott C. Wagner, MD
From the Department of Orthopaedic
Surgery, Walter Reed National Military
Medical Center, Bethesda, MA.
Correspondence to Dr. Wagner:
[email protected]
None of the following authors or any
immediate family member has
received anything of value from or has
stock or stock options held in a
commercial company or institution
related directly or indirectly to the
subject of this article: Dr. Fernicola,
Dr. Elsenbeck, Dr. Grimm, Dr. Pisano,
and Dr. Wagner.
The views expressed in this article are
those of the authors and do not reflect
the official policy of the Department of
Navy, Department of Army,
Department of Defense, or US
Government. The authors are
employees of the US Government.
This work was prepared as part of
their official duties, and as such, there
is no copyright to be transferred.
J Am Acad Orthop Surg 2020;28:
37-43
DOI: 10.5435/JAAOS-D-18-00475
Copyright 2019 by the American
Academy of Orthopaedic Surgeons.
January 1, 2020, Vol 28, No 1 37
Copyright © the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.

gram-positive organisms, which re-
main the most common cause of SSIs.
8
Despite an increased focus on
appropriate antibiotic stewardship,
antibiotic resistance continues to
increase, leading to more frequent
methicillin-resistant Staphylococcus
aureus infections. These infections
are associated with a higher mor-
bidity and mortality compared with
non–drug-resistant infections.
9
In an
effort to combat the increased preva-
lence of antibiotic-resistant infections,
many surgeons have begun using
lyophilized vancomycin powder
applied directly to the surgical
wound. Intrawound application al-
lows for a very high drug concen-
tration localized within the target
site, thereby avoiding systemic
absorption, and limiting the side ef-
fects of systemic dosing, such as
nephrotoxicity. Although the use of
antibiotic powder has been exten-
sively studied for use in spinal sur-
gery, there remains a paucity of
literature focused on the efficacy of
topical antibiotic application in
other areas of orthopaedic surgery.
10
The purpose of this article, therefore,
is to provide a concise and coherent
systematic review of the literature on
the efficacy of topical antibiotic
application.
Methods
The guidelines of Preferred Reporting
Items for systematic Reviews and
Meta-Analyses were followed for
conducting a systematic review.
Data Source
Electronic searches were conducted
on Ovid, MEDLINE, and PubMed
using a combination of the following
search terms: “orthopaedic antibiotic
topical”and “orthopaedic vanco-
mycin powder”and “orthopaedic
local antibiotics.”Studies were lim-
ited to articles published in English,
with inclusion of studies published
or accepted for publication before
May 2018. Study eligibility was inde-
pendently determined by reading the
title and abstracts by two authors. After
abstract screening, studies meeting the
eligibility criteria underwent a full-text
review. Articles were also retrieved for
abstracts that did not provide adequate
information for inclusion or exclusion.
Any study failing to meet eligibility after
full-text review was excluded, and ref-
erences from each full-text article were
similarly reviewed for inclusion eligi-
bility. Discrepancies in the selection
process were resolved through dis-
cussion and consensus among the re-
viewing authors.
Inclusion and Exclusion
Criteria
We included prospective and retro-
spective studies that described the
topical administration of antibiotic
powder within a surgical wound for
both adult and pediatric patients.
Studies included patients undergoing
any type of extremity or pelvic sur-
gery. Studies were excluded if the
antibiotic powder was mixed with
cement to be used as either a spacer or
beads or if the study involved spine
procedures.
Analysis
Quantitative statistical analysis was
not possible because of the significant
heterogeneity in the study design and
surgical procedures. Data from
included studies were publication
year, study design, number of pa-
tients, and type of surgeries per-
formed, amount of antibiotic powder
used, and infection rates: superficial
and deep infection rates were
included if specifically reported, as
well as complications/adverse events.
Results
After initial query of all databases
and removal of duplicates, the initial
search revealed 178 citations. One
hundred fifty-nine were removed
after evaluation of the abstract. Seven
studies were excluded because they
were review articles, one because it
was the protocol description of a
large prospective study, and the other
because it did not report any used
statistical methods (Figure 1). In
addition, one unpublished (but
accepted) manuscript was also
included. Overall, 11 studies met the
inclusion criteria. All were level III or
IV retrospective studies. Summary of
the included studies is illustrated in
Table 1.
Discussion
The use of intrawound vancomycin
powder was first reported almost 30
years ago in cardiothoracic surgery.
The powder was mixed with topical
thrombin and applied to the cut edges
of the sternum; this described tech-
nique yielded lower rates of sternal
infection compared with historical
controls (0.45% versus 3.6%).
21
The
application of topical antibiotic
powder has been studied extensively
in the spine literature, with most
studies demonstrating a reduction
of SSI with its use.
10,22,23
Haimoto
et al
24
compared the outcomes of
suprafascial vancomycin powder
application among patients under-
going posterior spinal fusion. Com-
pared with controls, patients who
received 1 g of topical vancomycin
powder demonstrated significantly
lower infection rates (zero versus
5.6%, P,0.001) without any
reported adverse vancomycin-
associated reactions. Although
administering vancomycin directly
into the wound affords localized
supratherapeutic drug concentration
without systemic toxicity, the
potential for cytotoxicity to bone at
the site of fusion remains concern;
however, in a recent study compar-
ing multiple antibiotic effects on
Intrasite Antibiotic Powder
38 Journal of the American Academy of Orthopaedic Surgeons
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osteoblast cytotoxicity, vancomycin
was found to be one of the least toxic
antibiotics tested.
25
Several studies have evaluated
the effect of vancomycin on in-
strumented fusions, but none have
reported any increased rates of
pseudarthrosis.
22,23,26,27
Similar to
concerns for pseudarthrosis in the
spine, the concern for local osseous
cytotoxicity continues to cause
trepidation in extremity surgery. A
paucity of literature exists to further
elucidate the effect antibiotic pow-
der may have on fracture healing,
arthrodesis, or bony ingrowth.
Wukich et al
13
investigated the use of
vancomycin powder in foot arthro-
desis procedures and concluded that
there was no effect on fusion rates.
Similarly, Singh et al
14
were able
to demonstrate favorable rates of
osseous healing after application of
vancomycin powder in open reduc-
tion and internal fixation (ORIF)
procedures for tibial plateau and
pilon fractures. Although topical
application creates a high local drug
concentration, the duration of this
supratherapeutic concentration re-
mains unknown. In a femur fracture
rat model, animals treated with local
vancomycin powder versus IV ad-
ministration demonstrated markedly
higher drug concentration at the site
for 48 hours, but by 96 hours, the
vancomycin was no longer detect-
able.
28
Unfortunately, no in vivo trials
are conducted to further investigate
the pharmacokinetic profile of topical
vancomycin application in patients
undergoing extremity surgery.
The study by Mohammed et al
11
was the lone nonorthopaedic study
we included because it included pa-
tients undergoing extremity (aorto-
femoral or infrainguinal) vascular
procedures. However, given that the
inguinal region is often an area for
concern regarding infection and is
often involved in orthopaedic proce-
dures, we felt that it warranted inclu-
sion. In addition to demonstrating a
statistically significant decrease in the
infection rate of 25.1% in the control
group to 17.2% in the treated group
(P= 0.49), primarily from a decrease
in superficial infections, 18.9% in the
control group versus 11.5% in the
treated group (P= 0.033), they also
failed to show a difference in aseptic
wound dehiscence, which has been a
concern when using vancomycin
powder in superficial wounds.
Although most of the included
studies involved the lower extremity,
the study by Yan et al
12
evaluated
infection rates in the upper extrem-
ity, specifically after open release of
posttraumatic elbows. Overall, six
patients of 93 patients in the control
group developed an SSI: two were
superficial and four were deep,
whereas no patients in the vanco-
mycin group had an SSI. The van-
comycin group had markedly shorter
surgical times compared with the
control group (154 minutes [range:
98 to 243 minutes] versus 176 mi-
nutes [range: 116 to 251 minutes],
P,0.001). In addition, they re-
ported that infected patients
demonstrated decreased preopera-
tive range of motion compared with
the control group as a whole and the
vancomycin group (16°[range 0°to
40°] versus 36°[range 0°to 73°]
versus 40°[range 0°to 74°]).
Although the authors did not com-
ment on the clinical significance of
this finding, patients with decreased
preoperative range of motion may
have required more extensive surgi-
cal release. As the vancomycin group
also had significantly shorter opera-
tive time, the results with regard to
decreased infection rates may be
confounded. External fixators were
used at similar rates in both the
control and vancomycin groups,
with no statistically significant dif-
ference in the rate of pin tract in-
fections. Interestingly, none of the
patients with pin site infections had a
concomitant wound infection. By the
time of final follow-up, no signifi-
cant difference was found in range of
motion or functional scores between
the two groups, as well as no dif-
ference in perioperative complica-
tions such as peripheral neuritis,
narcotic dependence, or signs of
nephrotoxicity.
Figure 1
PRISMA flow diagram.
Stephen D. Fernicola, MD, et al
January 1, 2020, Vol 28, No 1 39
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Table 1
Summary of Infection Rates for All Included Studies
Author/
Year
Study Design/
LOE
No.
of
Pts
Infection Rate
Antibiotic
Group
Infection Rate
Control Group Procedure Powder Used
Mohammed
et al,
2013
11
Retrospective
level III
454 1. Total 17.2%
(P= 0.049)
2. Superficial
11.5%
(P= 0.033)
3. Deep infection
5.7%
(P= 0.692)
1. Total 25.1%
2. Superficial
18.9%
3. Deep
infection
6.1%
Aortofemoral or
infrainguinal
procedures
Vancomycin
Yan et al,
2014
12
Retrospective
cohort level III
272 1. Total: zero
(P= 0.0027)
2. Superficial:
zero
3. Deep
infection: zero
1. Total 6.45%
2. Superficial
2.2%
3. Deep 4.3%
Open elbow
release
for posttraumatic
fibrosis
1 g vancomycin
Wukich et al,
2015
13
Retrospective
case-control
level III
92 1. Superficial
2.5%, P=
0.2734
2. Deep 2.5%,
P,0.05
1. Superficial
6.2%
2. Deep 12.4%
Multiple foot and
ankle procedures
in patients with
diabetes
0.5-1 g vancomycin
Singh et al,
2015
14
Retrospective
level III
93 1. Total 10%
P= 0.68
2. Superficial 0%
P= 1.0
3. Deep 10%
P= 1.0
1. Total 25.3%
2. Superficial
8%
3. Deep 16.8%
Plateau or pilon
ORIF
1 g vancomycin
Lawing et al,
2015
15
Retrospective
level III
351 1. Total 9.5%
(P= 0.010)
2. Deep 6.0%
(P= 0.011)
1. Total 19.7%
2. Deep 14.2%
Open fractures 80 mg tobramycin
or gentamicin
Khatri et al,
2017
15
Retrospective
level III
115 1. Total 9.8%
(P= 0.771)
2. Superficial
1.9%
3. Deep 7.8%
1. Total 12.5%
2. Superficial
3.1%
3. Deep 9.4%
TKA Vancomycin
Owen et al,
2017
16
Retrospective
level III
140 1. Total 4.2%
(P= 0.04)
1. Total 14.5% Pelvic and
acetabular
OORIF
Vancomycin and
tobramycin
Otte et al,
2017
17
Retrospective
level III
1,640 1. Total 1.57%
(P= 0.0479)
1. Total 0.49% TKA, RTKA,
THA, RTHA
Vancomycin
Pavey et al,
2018
18
Retrospective
level III
223 1. Total 17%
P= 0.03
1. Total 30% Lower extremity
amputations
Vancomycin
Dial et al,
2018
19
Retrospective
level III
265 1. Total 1.5%
2. Superficial
0.7% (P=
0.603)
3. Deep 0.7%
(P= 0.031
1. Total 7.0%
2. Superficial
1.5%
3. Deep 5.5%
DA THA 1 g vancomycin
intracapsularly, 1 g
extracapsularly
Winkler et al,
2018
20
Retrospective
level III
744 1. Total 2.66% 1. Total 8.16% TKA, RTKA,
THA, RTHA
2 g vancomycin
intracapsularly
DA THA = direct anterior total hip arthroplasty, LOE = level of evidence, RTHA = revision total hip arthroplasty, RTKA = revision total knee
arthroplasty, THA = total hip arthroplasty, TKA = total knee arthroplasty.
Intrasite Antibiotic Powder
40 Journal of the American Academy of Orthopaedic Surgeons
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Wukich et al
13
evaluated the effi-
cacy of vancomycin application
among patients with diabetes who
underwent a variety of foot and
ankle procedures. Patients received
between 500 and 1,000 mg of topical
vancomycin powder in all surgical
wounds both deeply and in the
subcutaneous tissue. Patients who
received vancomycin powder had a
73% decrease in overall infections,
including an 80% decrease in deep
infections, which was statistically
significant. In addition, three pa-
tients in the control group would
eventually require an amputation for
infection eradication; two patients
required a transtibial amputation
and one required a minor foot am-
putation. No patients in the vanco-
mycin group went on to more
proximal levels of amputation.
The study by Singh et al
14
evaluated
high-risk patients sustaining high-
energy periarticular tibial fractures.
They failed to demonstrate a signif-
icant reduction in either superficial
or deep SSIs. Half of the 14 patients
who developed a deep SSI in the
control group had open injuries, and
the single deep SSI in the vancomycin
group was also and open injury. The
cultures obtained from the single
infected patient in the vancomycin
group failed to grow any micro-
organisms by 6 months. The culture
data for the control group are as
follows: six methicillin-sensitive
S. aureus, four methicillin-resistant
S. aureus, one Staphylococcus epi-
dermidis, and three had no data
available. Although an overwhelming
percentage of infections from elective
surgeries can be traced to the patient’s
skin flora, open fractures result in
exposure to the environment and
therefore lead to a different infection
profile, including gram-negative bac-
teria and atypical bacterial or fungal
infections. Although they failed to
demonstrate a significant reduction in
either superficial or deep SSIs because
this was an initial pilot study, the
vancomycin group only included 10
patients, which limits the conclusions
that can be made from this study. The
authors conclude that in these sit-
uations, vancomycin powder alone
may not be best suited for preventing
deep SSIs.
The study by Lawing et al
15
is the
only study to use aminoglycosides as
their topical antibiotic. This study
evaluated all open fractures except
for fractures distal to the metacarpal,
or in which surgery was delayed
beyond 36 hours, or in which the
patient had a known systemic
infection at the time of surgery.
Following closure after irrigation
and débridement with ORIF, 80 mg
of tobramycin or gentamicin was
dissolved in 40 mL of saline and
injected deep to the fascia around the
implant. The total infection rate in
the intervention group at 9.5% (16
of 168) was significantly lower than
in the control group (19.7%, 36 of
183) (P= 0.010). When comparing
only the deep infections, the infec-
tion rate in the control group was
14.2% (26 of 183) compared with
6.0% (10 of 168) in the intervention
group (P= 0.011) After multivariate
analysis, the authors found admin-
istration of local antibiotics to be an
independent predictor of lower
infection rates in all infections (odds
ratio [OR] 2.6 [95% confidence
interval [CI], 1.2 to 5.6]; P= 0.015)
and deep infections only (OR 3.0
[95% CI, 1.1 to 8.5]; P= 0.034). In
addition, the use of local antibiotics
did not demonstrate any effect on
nonunion rates between the control
and treatment groups (15.5% versus
14.3%, respectively, P= 0.881).
Owen et al
16
recently published a
case-control series evaluating 140
patients with pelvic ring or acetab-
ular fracture treated with ORIF.
Patients who were treated in the first
10 months were retrospectively
enrolled in the control group, with
all surgeons adding 1 g of vanco-
mycin and 1.2 g of tobramycin to the
surgical wound on closure for the
subsequent 10 months. No differ-
ence was found with regard to age,
race, sex, prevalence of diabetes,
body mass index, tobacco use,
approach used, or mean procedure
length between the two groups. They
found a lower infection rate of 4.2%
(3 of 71) in the treatment group
versus 14.5% (10 of 69) in the
control group (P= 0.24). The risk of
infection was 78% lower in the
treatment group, although this
finding did not reach significance
(OR 0.22, 95% CI, 0.02 to 1.18).
When controlling for the amount of
surgical blood loss, however, a sig-
nificant association was found
between the use of the local antibiotics
and a lower infection risk in patients
with less than 1 L of blood loss (OR
0.10, 95% CI, 0.01 to 0.80).
Another recent study
18
evaluated
the effect of topical vancomycin on
rates of SSIs in patients undergoing
initial or revision combat-related
lower extremity amputations. The
authors found a 13% absolute risk
reduction in deep infections in pa-
tients receiving intrawound vanco-
mycin powder (17% versus 30%,
P= 0.03). In revision amputation
surgery, there was a 16% overall
decrease in infection (13.8% versus
29.8%, P= 0.037) and 25% for
previously infected limbs (17% ver-
sus 1.42%, P= 0.01). The subse-
quent number needed to treat to
prevent one additional deep infection
in amputation surgery was eight in
initial amputations, seven in revision
amputations, and four for revision
amputation surgery on previously
infected limbs.
Our search also extended to the
literature for total joint arthroplasty.
Periprosthetic joint infection (PJI)
after a total joint arthroplasty is a
devastating complication, and thus,
significant efforts have been directed
toward prophylaxis against infec-
tion, including several studies exam-
ining the use of topical antibiotics.
Stephen D. Fernicola, MD, et al
January 1, 2020, Vol 28, No 1 41
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