Antibiotic prophylaxis and prevention of wound infections following implant removal after foot, ankle and lower leg fractures

Imagine: a year ago you broke your ankle and were operated on. Full recovery
took many weeks. Now the plate is removed, supposedly a
minor procedure. However, 3 days after the operation you get a wound infection,
necessitating a hospital admission, a re-operation and
antibiotics. The healing process takes several weeks, with all its
inconveniences, like changing wound dressings and absence from work.
This research proposal is about prevention of such infections.
Patients with lower leg fractures are treated either conservatively with a cast
or with the use of implants (osteosynthesis material) to restore
anatomy and function. The implant can be removed at a later stage. The
indications for implant removal in adult patients include
symptomatic hardware (i.e. pain, thin overlying skin and restricted motion),
failure of the implant (breakage, loosening), or a persistent
infectious complication of the index procedure (infection or fistula). Some
patients choose to have implants removed for no specific reason.
In the Netherlands each year about 18,000 surgical implant removals are
performed after fracture healing, of which 30-80% from the foot,
ankle and lower leg region. In contrast to surgical fracture fixation with
metal implants, antibiotic prophylaxis is not routine practice prior to
implant removal. This is because, according to the Centres for Disease Control
and Prevention (CDC) classification of surgical wounds,
implant removal is considered a *clean* procedure. For *clean* procedures the
rate of wound infections should be less than 5% and no
benefit of preoperative antibiotics has been seen. However, rates of 12%
following implant removal, specifically after foot, ankle and/or
lower leg fractures, have been observed both by us and others. This implicates
that implant removal should not be seen as *clean*
procedure but rather as *clean-contaminated* or in some patients even as a
*contaminated* procedure. Consequently, preoperative
antibiotics might be beneficial to reduce the incidence of infectious
complications. Use of a single gift of prophylactic antibiotics has been
shown to be as efficient as repeated prophylactic gifts. Moreover, a single
gift is preferred since it avoids development of antibiotic
resistance. In current practice, surgeons decide upon themselves if antibiotics
are administered preoperatively, which is based on expert
opinion as no evidence based guideline exists. This results in undesirable
practice variation.

In light of the above, our objective is to study the (cost-) effectiveness of a
single intravenous gift of antibiotic prophylaxis with a first
generation cephalosporin prior to implant removal following surgical fixation
of foot, ankle and/or lower leg fractures. We will examine the
effects in terms of the rate of postoperative wound infections (primary
outcome), health related quality of life, functional outcome and health
care costs (secondary outcomes). In addition, we will create an evidence based
guideline.

Multicentre, double-blind, randomized, placebo controlled trial. The study will
be conducted according to the principles of the Declaration of
Helsinki, the Medical Research Involving Human Subjects Act (WMO), Good
Clinical Practice Guidelines (GCP) and other applicable
(inter)national regulatory requirements.

Patients will be randomly assigned to implant removal with administration of a
single dose intravenous antibiotic prophylaxis (cefalozin) or a
matching 10 cc NaCl 0.9% by use of a web-based randomization site. The vial
will administered 30 minutes pre-operatively (t=0). During surgery a bacterial
swab will be taken from the implant. Patients will return at least once to the
outpatient clinic postoperatively as usual (t<30 days).

The risks in this study are acceptable for the patients participating in this
study, as cephalozin is already used as a prophylactic antibiotic in
current practice in open reduction and internal fixation of lower leg, ankle
and foot fractures.
The prolonged supervision of patients does not harm patients in any way and can
only contribute to better patient management.