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Contents lists available at ScienceDirect

Injury
journal homepage: www.elsevier.com/locate/injury

Prevention of infection in open fractures: Where are the pendulums

now?
Markus Rupp, Daniel Popp, Volker Alt∗
Department of Trauma Surgery, University Medical Centre Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany

a r t i c l e i n f o a b s t r a c t

Article history: Soft tissue management and fracture fixation including initial external fixation in Gustilo-Anderson type
Accepted 22 October 2019 II and type III open fractures are cornerstones in the treatment but details on timing and type of wound
Available online xxx
closure, irrigation and debridement, systemic and local antibiotics, antimicrobial-coated implants and the
use of Bone Morphogenetic Protein-2 remain controversial. This article looks at current clinical evidence
of these items for the management of open fractures. Timing of debridement and wound closure remains
critical. Early debridement by an experienced team within 24 h seems adequate while gross contam-
ination, a devascularized limb, a multi-injured patient and compartment syndrome require immediate
surgical intervention. Wound closure during the first surgery was shown to result in reduced rates for
infections and nonunion. If soft-tissue reconstruction is needed, it should be performed within the first
7 days. Regarding types of irrigation fluid, antiseptic and antibacterial solutions did not prove to be su-
perior to saline. High pressure irrigation has not been demonstrated to be beneficial whereas antibiotic
administration as soon as possible has been proven to be favorable. Administration of more than 72 h
was not superior to shorter systemic antibiotic intervals. For Gustilo-Anderson type I and II, broad spec-
trum antibiotic therapy is reasonable. Additional aminoglycosides for broader coverage are recommended
in Gustilo-Anderson type III fractures. There is newer literature on the beneficial effects of the use of
local antibiotics, e.g. by antibiotic beads. Coating of internal fixation devices is a modern approach to im-
prove infection prophylaxis and gentamicin-coated implants have been demonstrated to be safe in clinical
application. Vacuum assisted closure (VAC) could not evidence negative pressure wound therapy to re-
duce infection risk, improve self-rated disability or quality of life in open fractures, however, enhance
treatment costs. Recombinant human bone morphogenetic proteins (rhBMP)-2 showed promising data in
Gustilo-Anderson type III open tibial shaft fractures with lower rates of invasive secondary procedures. In
conclusion, there is evidence for thorough debridement and irrigation with saline, early soft tissue cover-
age and the use of systemic and local antibiotics. Except for a short-term soft tissue coverage VAC seems
not to be beneficial and rhBMP-2 is an additional tool in Gustilo-Anderson type III open fractures.
© 2019 Elsevier Ltd. All rights reserved.

Introduction
Open fractures have plagued mankind over hundreds of thou-
sands of years with high mortality rates until the key discoveries
of antibiotics on the one hand and of surgical treatment by de-
bridement, irrigation and immobilization on the other hand during
the 20th century [1]. Amputation until then was generally deemed
necessary as a lifesaving surgical procedure to avoid haemorrhage,
infection and subsequent sepsis [2,3].
Today, open fractures are still difficult to treat. Especially infec-
tion is an often-encountered challenge for surgical care. Depend-
ing on injury severity infection rates range from 1.8% in Gustilo-
∗
Corresponding author.
E-mail address: volker.alt@ukr.de (V. Alt).
Anderson type I fractures to 42.9% in type IIIB open tibial fractures
[4,5]. Thus, prevention of infection in open fractures is of utmost
importance. Soft tissue management and fracture fixation includ-
ing initial external fixation in Gustilo-Anderson type II and type III
open fractures with later conversion to internal fixation are gen-
eral accepted treatment principles in open fracture management
(Fig. 1). Nevertheless, nonunion rates up to 54% and amputation
rates up to 17.6% in Gustilo-Anderson type IIIB open tibial fractures
indicate need for treatment optimisation [4]. Details on timing and
type of wound closure, irrigation and debridement, systemic and
local antibiotics, antimicrobial-coated implants and the use of Bone
Morphogenetic Protein-2 remain controversial. This is most likely
determined by the lack of high-level prospective trials. Therefore,
this work summarizes the current state of each different treatment
component based on current literature.

https://doi.org/10.1016/j.injury.2019.10.074
0020-1383/© 2019 Elsevier Ltd. All rights reserved.

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2 M. Rupp, D. Popp and V. Alt / Injury xxx (xxxx) xxx

Fig. 1. Standard treatment for a Gustilo-Anderson type II open distal femoral shaft fracture. (A) Open wound of about 8 cm directly over the fracture site with exposure of the
bone through the skin. (B) Immediate debridement and irrigation of the wound with wound closure and application of an external fixator (patient has an additional closed
tibial shaft fracture). (C) Post-operative X-ray with good reduction of the fracture and correct application of the external fixator. (D-E) X-rays in 2 planes after conversion from
external to internal fixation on day 7 with retrograde nailing of the femur and antegrade nailing of the tibial fracture. (F-G) X-rays in two planes with good consolidation of
femoral shaft after 3 months with good skin and soft tissue conditions after uneventful wound healing after primary closure.

Timing of wound debridement, wound closure and modes of
irrigation
Surgical wound management in open fractures is controversially
discussed. Nevertheless, it is generally accepted that timely sur-
gical management is of paramount importance. The “6 h rule”,
which advocates surgical debridement within the first 6 h after
trauma was introduced by Friedrich in the 19th century supported
by his findings that 6 h turned out to be critical for massive bac-
terial replication [6]. Thus, he believed that surgical debridement
should be carried out within 6 h after injury. Several clinical stud-
ies attempted to confirm this experimental findings but failed to
find evidence supporting comparable threshold such as five, eight
or twelve hours regarding infection or nonunion rates [7–9]. Both
clinical and experimental data demonstrate a time dependent in-
crease in infection rates. Hull and co-workers determined an in-
crease of infection risk of 3% per hour delay of surgical debride-
ment in Gustilo-Anderson type II and III tibial fractures [10]. Penn-
Barwell and colleagues were able to demonstrate that a delay of
surgical debridement but even more a delay in systemic antibiotic
administration reduce infection in an open fracture model in rats
[11]. Hence, early debridement by an experienced team seems ad-
vantageous performed on a semi-elective basis within 24 h. How-
ever, compartment syndrome, devascularization of the limb and
gross contamination require immediate surgical care [12].
As well as timing of initial surgical debridement, so timing
of wound closure is controversially discussed. Historically, con-
cerns about deep infection caused by Clostridium species and other
anaerobic organisms in battlefield wounds led to the practice that
wounds in open fractures were left open [13]. However, in the
last years primary wound closure could be evidenced to be ben-
eficial resulting in lower deep infection rates and less nonunions
for Gustilo-Anderson type I – IIIa fractures. Scharfenberger et al.
demonstrated fewer deep infections (4% vs. 9%) and nonunions
(13% vs. 29%, p < 0.001) in Gustilo-Anderson type I-IIIa frac-
tures when comparing immediate wound closure to a matched
cohort group with delayed soft tissue coverage [14]. Jenkinson
and co-workers described an even lower infection rate in Gustilo-
Anderson type I-IIIa fractures when treated with immediate clo-
sure (infection rate 4.1%; 95% confidence interval [CI], 0.86 to 11.5)
compared to delayed primary closure (infection rate 17.8%; 95% CI,
9.8 to 28.5, p = 0.0 0 01) [15]. For fractures requiring soft tissue re-
construction by flap coverage, Marco Godina reported low infection
rates of 1.5% after flap reconstruction within 72 h in compound
fractures of the lower extremities [16]. This ground-breaking work
already published in 1986 introduced the concept of emergency
free flap coverage, which is coined by the term “fix and flap”.
Recent studies underlined the success of Godinaś treatment ap-
proach. In fractures with severe soft tissue injuries requiring plas-
tic reconstruction early flap reconstruction within 7 days has been
associated with better clinical outcomes than a delay in plastic re-
construction by flap coverage. Higher infection rates have been re-
ported in patients treated by free flap coverage more than 7 days
after open tibial fractures (infection rate 27% within 7 days vs. 60%
after 7 days (p < 0.04)) [17]. Pincus and co-workers demonstrated
an increase of complications with a delay in flap coverage beyond
7 days (16.7% complication rate vs. 6.2%, p < 0.001, number needed
to harm = 10) [18].
Irrigation is another pivotal component of surgical wound man-
agement. Recently, the FLOW trial was initiated to answer the
question of the appropriate mode of irrigation and irrigation so-
lution. For this multicentre prospective randomized control trial
(RCT), 2447 patients at 41 sites were included. Three different
wound irrigation pressures as well as saline versus castile soap
for irrigation solution were compared. Primary endpoint was re-
operation for promotion of wound or bone healing and treatment

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of wound infection within a follow-up of 12 months. Reopera-
tion rates did not depend on irrigation pressures. One hundred
nine of 826 patients (13.2%) in the high-pressure group (>20 psi),
103 of 809 (12.7%) in the low-pressure group (5–10 psi) and 111
of 812 (13.7%) in the very-low-pressure group (1 to 2 psi) under-
went revision surgery. Meanwhile, reoperation was significantly
more frequent after use of soap irrigant compared to reoperation
rates in patients treated with saline (soap vs. saline: 128/1229 pa-
tients (14.8%) vs. 141/1218 (11.6%); (hazard ratio, 1.32, 95% CI, 1.06–
1.66; P = 0.01)) [19]. Patient reported outcomes during 12 months
follow-up did not depend on irrigation solutions as well as ir-
rigation pressure [20]. Thus, potential drawbacks of high pres-
sure irrigation with bacterial seeding into the intramedullary canal
[21] and myonecrosis of soft tissue [22] evidenced in animal exper-
iments could not be proven to be clinically relevant. Low pressure
irrigation, however, seems to be a viable and economical treatment
option. Clinical data comparing patient outcomes such as fracture
union, development of infection and healing of soft tissue wounds,
did not demonstrate an advantage of bacitracin solution compared
to nonsterile castile soap solution. Even significantly more wound
healing disturbances were observed in the antibiotic additive group
[23]. In a rat animal model of open fracture, saline and the antisep-
tics iodophor and hydrogen peroxide were compared for irrigation.
Saline was comparably effective and superior in minimizing ad-
verse wound inflammation compared to both antiseptics [24]. Toxic
effects against host tissue was reported for chlorhexidine as well.
A rebound effect of bacterial growth due to chlorhexidine induced
tissue damage has been reported [25]. Comparing saline with dis-
tilled water in a clinical prospective trial [26] and with tap wa-
ter in a preclinical porcine open fracture model [25] could demon-
strate comparable outcomes for both distilled as well as tap water
compared to saline solution. Despite intensive preclinical and clin-
ical research and daily clinical relevance, no reliable data for the
appropriate volume of rinsing solution exists.
Systemic antibiotic prophylaxis
Administration of systemic antibiotics is an essential part of the
surgical management protocol for open fractures. A Cochrane re-
view of 2004, which included 7 studies with in total 913 patients
of randomised or quasi-randomised controlled trials, proved a pro-
tective effect of systemic antibiotics against early infection (risk
ratio (RR) 0.43 (95% CI, 0.29–0.65), number needed to treat = 13
(95% CI, 8–25)). Systemic antibiotics were all penicillin derivates
or first generation cephalosporines active against gram-positive or-
ganisms. However, the issue of optimal duration of prophylaxis
and its effectiveness as well as potential adverse effects could not
be explored [27]. A recent review by Chang and co-workers con-
firmed systemic antibiotics to reduce risk of infection in open frac-
tures (RR = 0.37; 95% CI, 0.21–0.66; absolute risk reduction = 9.6%;
95% CI, 5.2–12.1%). The question of short (single dose, double dose,
one day) versus longer (three to five days) systemic antibiotic ad-
ministration for prophylaxis was addressed as well. No signifi-
cant difference could be determined comparing both different sys-
temic antibiotic treatment strategies (RR = 0.97; 95% CI, 0.69–1.37)
[28]. In their review and meta-analysis Messner et al. came to the
same conclusion. In addition to duration of antibiotic prophylaxis,
the authors compared severity of soft tissue damage. For Gustilo-
Anderson type I and II (more than 72 h antibiotic treatment = 6%,
95% CI, 3.3%–9%; less than 72 h treatment = 4%, 95% CI, 1.8%−7%),
p = 0.52), as well as Gustilo-Anderson type III open fractures (more
than 72 h antibiotic treatment = 21.3%, 95% CI, 13%−31%; less than
72 h treatment = 17.7%, 95% CI, 12.5%−23.5%) (p=0.39)), no bene-
fit of prolonged antibiotic administration of 72 h or longer could
be evidenced compared to antibiotic administration up to 72 h.
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3
Sub-group analysis of even 24–48 h antibiotic regimens were even
equivalent to prolonged more than 72 h regimens [29].
Regarding timing of initial antibiotic prophylaxis, both clini-
cal and experimental evidence support an early as possible ad-
ministration of systemic antibiotics. In 137 patients with type III
open tibial fractures, time of antibiotic administration greater than
66 min was predictive for infection [30]. This data strongly sug-
gests immediate administration of antibiotics during primary care
at the accident site prior to inpatient admission of the injured.
For choice of antibiotics in Gustilo-Anderson type I and II frac-
tures systemic antibiotic coverage directed at gram-positive or-
ganisms is recommended. For Gustilo-Anderson type III fractures
broader, additional gram-negative antibiotic coverage is advocated.
If faecal or clostridial contamination is suspected, high dose peni-
cillin is considered suitable for additional prophylaxis [31]. Studies
with low level of evidence due to their retrospective design, how-
ever, demonstrated that additional use of aminoglycoside or gly-
copeptides does not result in change of incidence of wound in-
fection or need for hardware removal [32,33]. Even a higher rate
of acute kidney injury was demonstrated for additional aminogly-
coside use by Bankhead-Kendall and colleagues (10% acute kid-
ney injury vs. 4% comparing cephalosporine + aminoglycoside vs.
cephalosporine alone) [32]. Systemic piperacillin/tazobactam pro-
phylaxis was not inferior to a combined cefazolin plus gentam-
icin prophylaxis in Gustilo-Anderson type III open fractures re-
garding surgical site infections after 30 days, nonunion, death,
as well as rehospitalization rates at one year [34]. Culture re-
sults of deep tissue samples after initial debridement and revi-
sion surgery of Gustilo-Anderson type III fractures demonstrated
a high level of contamination. Intriguingly, the number of evi-
denced pathogens resistant against broad spectrum antibiotic ther-
apy (amoxicillin + clavulanic acid) was considerable (47% at initial
surgery and 88% at first revision surgery, respectively). Neverthe-
less, favourable outcome in Gustilo-Anderson type III injuries was
possible by surgery combined with antibiotic prophylaxis (80% vs.
20% amputation) [35]. Appropriate surgery as a predominant fac-
tor but also microorganisms not resulting in infection after open
fractures are possible explanations for this observation.
Local antibiotic prophylaxis
Morgenstern and co-workers recently performed a systemic lit-
erature review with a pooled data analysis on this controversial
topic [36] and compared standard systemic antibiotic treatment
with standard antibiotic prophylaxis plus additional local antibi-
otic prophylaxis. In 2738 patients, an overall infection rate of 7.9%
could be determined. Patients treated with additional local antibi-
otics suffered from infection in 4.6%, while infection occurred in
16.5% of all patients with only systemic antibiotic prophylaxis. Due
to heterogenous groups, low level of evidence in the primary stud-
ies and potential risk of bias, it was supposed to interpret these
results with caution [36]. Different forms of local antibiotic ap-
plication are one factor which are reason for this heterogenous
groups. The most popular carrier for local antibiotics are antibi-
otic impregnated PMMA (poly(methyl methacrylate)) bead chains,
which have been developed by the pioneering Klaus Klemm in
the 1970s [37]. Since PMMA bead chains are not biodegradable,
removal of the bead-chains requires a second surgery. However,
antibiotic-loaded beads can be applied during initial irrigation, de-
bridement and external fixation application for local antibiotic pro-
phylaxis and taken out during conversion from external to inter-
nal fixation (Fig. 2). Development of resistant bacterial strains due
to antibiotic concentrations below the minimal inhibitory concen-
tration of bacteria has been reported in long term use of several
weeks or even months [38]. Furthermore, total antibiotic elution
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Fig. 2. X-ray series of gentamicin-loaded PMMA beads in a Gustilo-Anderson type II open tibial shaft fracture. (A-B) Application of commercially available gentamicin loaded
PMMA beads close to the fracture site through the open wound after irrigation and debridement with external fixation and primary wound closure. (C-D) Conversion from
external fixation to antegrade unreamed nailing with removal of the PMMA beads. (E-F) Good consolidation of the fracture 4 months after nailing.
in non-biodegradable PMMA bead chains is low, since elution is a
surface effect [39].
To overcome the limitations related with PMMA bead chain ap-
plication, biodegradable carriers for local antibiotic delivery have
been developed. Collagen fleeces are most widely used. Fast release
of 95% of the contained antibiotic within the first 1.5 h [40] and
consecutive release of antibiotics during resorption, which usu-
ally takes 8 weeks, are the pharmacokinetic characteristics [41].
Calcium sulphate based antibiotic carriers are another completely
resorbable therapy option. However, evidence for open fractures
remains low. Only two case series have been published using cal-
cium sulphate pellets as antibiotic carrier in open fracture treat-
ment [42,43]. Local application of vancomycin powder without
carrier seems to be an auspicious therapy option. In spinal surg-
eries and acetabular fractures surgical site infections could be pre-
vented [44,45]. For extremity fractures no beneficial effect could
be evidenced in a small sample size retrospective study [46]. In
contrast, OT́oole et al. recently demonstrated a beneficial effect of
local use of vancomycin powder. In their prospective RCT which
included 984 patients suffering from either tibial plateau or pilon
fractures treated by plate or screw fixation additional application
of 10 0 0 mg vancomycin powder during fracture care reduced in-
fection rates from 10.3% in the control group to 6.7% in the inter-
vention group. Pathogen analysis revealed similar rates in gram-
negative infections (2.1% in the control group vs. 2.6% for those
who received vancomycin powder) compared to a drop in the in-
fection rate of gram-positive infections (7.8% in the control group
vs. 3.7% in the intervention group) [47]. This study confirmed ben-
eficial effects of local vancomycin powder application to open frac-
tures, which previously has been demonstrated in open fracture
animal models [48,49]. A significantly lower infection rate in open
fractures by injecting an aqueous aminoglycoside as adjunct to
systemic antibiotic has been reported as well by Lawing and co-
workers A significant reduction of infection from 19.7% in the con-
trol group compared to 9.5% in the local aminoglycoside group was
found in their therapeutical level III interventional trial [50].
Vacuum assisted closure therapy
The technique of vacuum assisted closure therapy has been suc-
cessfully introduced in the 1990s [51]. For temporary wound clo-
sure in open fractures, vacuum assisted closure (VAC) therapy also
known as negative pressure wound therapy (NPWT) is a suitable
form of dressing. Theoretically, vacuum by suction of a pump re-
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moves blood and wound fluids, which usually are collected in the
wound. In addition, negative pressure promotes formation of gran-
ulation tissue [52]. Despite its potential clinical advantages, only a
few high-quality studies were initiated to examine the suggested
treatment benefits. Most recently the results of the prospective
randomized “UK Wound management of Open Lower Limb Frac-
tures” (UK WOLLF) trial in a study population of total 460 patients
with Gustilo-Anderson type II or III fractures of the lower limbs
did not show any significant difference in self-rated disability (Dis-
ability Rating Index score at 12 months (mean score 45.5 in the
NPWT group vs. 42.4 in the standard dressing group; mean dif-
ference −3.9; 95% CI, −8.9–1.2; p = 0.13), number of deep surgical
site infections (16 (7.1%) in the NPWT group vs. 19 (8.1%) for the
standard dressing group) and quality of life (difference in EuroQol
5-dimensions questionnaire, 0.02; 95% CI, −0.05–0.08; Short Form–
12 Physical Component Score, 0.5; 95% CI, −3.1–4.1; and Mental
Health Component Score, −0.4; 95%CI, −2.2–1.4) between patients
treated with VAC compared to patients treated with standard ster-
ile dressings [53]. These findings are in line with the results of
a systemic Cochrane review from 2018 assessing the effects of
NPWT for treating both open fractures and open wounds. Assess-
ment of 7 RCTs revealed no difference in open fracture wounds
healed at six weeks (RR 1.01 (95% CI 0.81–1.27). It could be con-
cluded that moderate-certainty evidence for NPWT exists to be
not cost-effective for open fracture wound treatment. It remained
uncertain, whether there is a difference in risk of wound infec-
tion, adverse events, time to closure or coverage surgery and pa-
tient related outcome measures comparing NPWT with standard
care [54]. Another systemic review tried to answer the question
if fewer infections and fewer flap procedures can be enabled by
application of NPWT in type IIIB Gustilo-Anderson fractures. Af-
ter inclusion of one RCT and 12 retrospective studies, it was not
convincingly clear if NPWT led to more infections [55]. Some evi-
dence, however, suggests NPWT resulting in fewer infections when
used in the acute phase after trauma [56,57]. Further, a reduction
of flap rates but an increase in local wound care including skin
grafting could be determined [55]. A post-hoc analysis of patients
in a RCT, which originally investigated wound irrigation in open
fractures, could demonstrate increased infection rates using NPWT
for all types of open fractures, independently from wound irriga-
tions and pressures for wound irrigation used [58,59]. In summary,
NPWT seems to facilitate soft tissue treatment in the challenging
acute posttraumatic phase. Based on the current literature, NPWT
serves as a suitable temporary solution for the first debridement
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and irrigation procedure if the wound cannot be closed primarily.
Beyond the indication as transitional wound coverage until defini-
tive wound closure, insufficient evidence is available in literature
to support or discourage NPWT in open fracture care.
Bone morphogenetic proteins
In the early 20 0 0s, the approval of recombinant human bone
morphogenetic proteins (rhBMP) 2 and 7 for open fracture (rhBMP-
2) [60] and tibial nonunions (rhBMP-7) [61] treatment was en-
couraging. The BMP-2 Evaluation in Surgery for Tibial Trauma
(BESTT) study, which was a randomized controlled trial in 450 pa-
tients with open tibial shaft fractures, demonstrated safety and ef-
ficacy of rhBMP-2 enclosed in an absorbable collagen sponge with
a lower need for secondary surgical intervention, faster fracture
healing and fewer infection rates of the group that was additionally
treated with 1.5 mg/ml rhBMP-2 compared to the standard of care
group with standard soft tissue management and intramedullary
nailing alone [60]. The higher percentage of patients treated with
a reamed nail in this 1.5 mg/ml rhBMP-2 group, which was deemed
to be beneficial for fracture healing, limited the overall positive
conclusion of this study. A subgroup analysis of two RCTs per-
formed by Swiontkowski et al. in 2006 [62] confirmed a signifi-
cant lower rate of invasive secondary procedures and a significant
lower infection rate in the 1.5 mg/ml rhBMP-2 compared to the
standard of care group in Gustilo-Anderson type IIIA and IIIB open
tibia fractures. In both studies distribution of patients treated with
a reamed nail (52.6% and 26% in the standard of care groups vs.
50% and 39.6% in the 1.5 mg/ml BMP-2 groups) were similar [62].
Another study of Aro et al. (2011) specifically studied the effects of
1.5 rhBMP-2 in reamed nailing for open tibia fractures. The results
showed a higher proportion of healed fractures after 13 weeks in
the rhBMP-2 compared to the control group, with no difference be-
tween the two groups after 20 weeks. There was a non-significant
higher infection rate in the rhBMP-2 (19%) compared to the con-
trol group (11%), which could not fully be explained by the au-
thors. This guided the European Medical Agency (EMA) to limit
the use of 1.5 mg/ml rhBMP-2 for the treatment of open tibia frac-
tures in adults as an adjunct to unreamed nail fixation. Our group
could show in a pooled data analysis from studies by Govender
et al. [60] and Swiontokowski et al. [62] that the use of 1.5 mg/ml
rhBMP-2 in Gustilo-Anderson type IIIA and B open tibia fractures
treated with an unreamed nail results in significant lower rates of
both secondary procedures (e.g. nail dynamization) and of more
invasive secondary procedures (e.g. bone grafting, fibula osteotomy,
nail exchange, re-osteosynthesis by plate) compared to the control
groups. Average fracture healing time was 228 days for patients
treated with BMP-2 and 266 days for the standard of care group
[63].
Coating of implants
One of the goals of antibiotic prophylaxis is to avoid biofilm
formation on metallic implants. Thus, antimicrobial functionalizing
of the implant surface is obvious. Different antimicrobial coatings
such as poly(d, l-lactide), silver and povidone-iodine have been
tested in clinical studies [64–70]. Except implants functionalized
with gentamicin coatings, none of the clinically tested coatings
have been used for open fractures. The clinically available gentam-
icin coating is based on a fully resorbable poly (D, L-lactide) ma-
trix which enables an initial burst release of 80% of gentamicin
within the first 48 h. This should obviate development of antibi-
otic resistance due to further subinhibitory gentamicin concentra-
tions [71]. Two case series reported favourable outcomes in 8 and
19 patients treated for open tibial shaft fractures, respectively. Us-
ing an unreamed intramedullary nail (UTN PROtect® (Depuy Syn-
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5
Fig. 3. Simplified representation of cornerstones in open fracture treatment beside
fracture stabilization. Debridement and irrigation as well as local and systemic an-
tibiotic prophylaxis are mandatory in open fracture care. VAC treatment should be
considered only as solution for early soft tissue coverage. Use of BMP-2 seems to
be beneficial in Gustilo-Anderson type III fracture while coatings of implants are
promising. However, randomized controlled trials are still missing.
thes, Switzerland) in patients suffering from open tibial shaft frac-
tures no infection after a one-year follow-up was reported in both
studies [64,66]. Later, a multicentre prospective case series with a
follow-up of 18 months was conducted with a total of 99 patients
treated with the poly (D, L-lactide) -gentamicin coated Expert Tibia
Nail (ETN PROtectTM , Depuy Synthes, Switzerland). Thirty-five pa-
tients underwent surgery for open fractures, the other cases were
closed fractures (n = 33) or revision surgeries. In 3 patients with
Gustilo-Anderson type III (A or B) tibial shaft fractures, surgical site
infections occurred [67]. A second case series of the use of the ETN
PROtectTM nails included 9 open tibial fractures. No deep infection
could be evidenced after 18 months follow-up [65]. Lower infec-
tion rates for silver coated megaprosthesis in tumoral prosthesis
surgery [68] and salvage revision arthroplasty [72] suggest clinical
application of silver coated implants in fracture care. However, no
clinical studies of silver coated implants in fracture care exist, yet.
Both the low level of evidence as well as few studies dealing with
promising implant enhancement by antimicrobial coatings in open
fractures implicate need of additional comparative studies.
Conclusion
For open fracture care, emergency treatment consists of early
systemic antibiotic prophylaxis, debridement of a senior sur-
geon and irrigation with saline. In addition to external fixation
in Gustilo-Anderson type III fractures wound closure should be
achieved whenever possible. In Gustilo-Anderson type IIIB frac-
tures a delay of soft tissue reconstruction by flap more than 7
days should be avoided. Systemic antibiotics should be adminis-
tered in any case and as soon as possible. Local antibiotic prophy-
laxis seems also to be beneficial. The use of rhBMP-2 results in a
lower rate of invasive secondary interventions in Gustilo-Anderson
type III fractures. In future, coatings of implants might help to
avoid complications (Fig. 3).
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