Reduction of surgical-site infection in hip and knee arthroplasty: the influence of perioperative mupirocin nasal ointment and chlorhexidine soap in a double-blind, randomized, multicentre, placebo-controlled study.

A primary infection after hip or knee prosthetics is one of the most feared
complication. There are two types of infections; superficial and deep.
The definitions according to PREZIES being talked about;
Superficial infections:
- On skin or subcutaneous tissue occur within 30 days after surgery
- There is septic effusion in the incision or pain / localized swelling /
redness / heat + positive wound culture or pain or tenderness / localized
swelling / redness, heat and open surgical wound culture is positive or not
cultured
Deep infections:
- Infection on deep tissue (fascia or muscle) occur within 1 year after surgery
- There is septic effusion from the deep incision or abscess or other sign of
infection in observation / reoperation or at least one of the following
clinical symptoms (pain, swelling, redness, warmth, fever> 38 and spontaneous
or surgically opened wound dehiscence and

Within Isala, the average infection rate (+ deeply superficial) over the period
2004-2012 for total hip arthroplasty os (THA) 3.32%, total knee arhtroplasties
(TKA) are infected in 1.98% of cases. When we focus on the deep infections then
3.25% of primary total hip and 1.87% of primary total knee become infected.
Nationwide, the percentage in the last 10 years is significantly lower, in 1.97
of hip replacement an infection is recorded. In 1.07% of cases there is a deep
infection.
Of the total knee prosthesis 1.4% (superficial + deep) of patients is diagnosed
as an surgical side infection, 0.83% is recorded as deep.

In this study we only focus on deep wound infections, because this patient
group should be treated with, surgical dibridement and long-term intravenous
antibiotics. Iff infection persists despite of antibiotic treatment and
re-operation. Then should the prosthesis be removed. This prosthesis infection
treatment is associated with high morbidity and costs. For the revision
surgeries is this a factor of 4 higher. This revision is so heterogeneous group
with respect to the variability in surgeries that it will not fall within the
rationale of this study.
This prosthesis infection is slightly more than 50% of the cases Staphylococcus
aureus (S. aureus), the causative agent, this percentage is also found in the
UK and US hospitals (1, 2).
More than 80% (5-7) of the post-operative S. aureus infections are taken from
the patient himself. Kalmus concluded that colonization with S. aureus causes
an increased risk of infection in orthopedic patient population (8). It is
therefore important to have free the patient pre-operative S. aureus. Mupirocin
containing ointment intranasally eradiceert S. aureus carriers, and is proved
to be effective for the prevention of wound infection in a case control study
(9). However, in a pair of RCT's is no decline in the number of infections
demonstrated within an orthopedic and general surgical patient population (10;
11). After a sub-analysis of the data showed that patients who were carrying S.
aureus, mupirocin nasal ointment or effective (10; 11). Slover concluded that
screening and perioperative eradication of S. aureus within the orthopedic
patient population is cost effective (12). Recently there has been in the BMJ
meta-analysis of 17 articles were published (13), it emerged the perioperative
eradication provides a reduction of wound infections in patients undergoing
orthopedic and cardiothoracic surgery. They also conclude that perioperative
treatment with mupirocin nasal ointment (Bactroban®) and
chlorhexidine-containing soap (Hibiscrub®) also gives a clear reduction in S.
aureus-related wound infections. In the discussion, it is stated that it is
heterogeneous groups of patients and therefore the results should be
interpreted with caution.
About one third of the Dutch population is colonized with S. aureus. In
addition, a portion varying colonized (30-60%) (9; 14-17), these patients can
therefore be missed by pre-operative screening for S. aureus. A preoperative
real-time polymerase-chain-reaction (PCR) on S. aureus is logistics vulnerable
and expensive.
Within cardiothoracic surgery Isala has over 10 years experience with the
prophylactic use of Bactroban® nasal ointment without neglecting the
development of resistance is seen. In addition, it is of course true that
resistance development using Bactroban® nasal ointment in patients Non carrier
is not at issue, because these patients no S. aureus carry, and this de facto
can not be resistant.
After 5 days Bactroban® use about 91% nasal carriage is suppressed and there is
no resistance seen (14). S. aureus may colonize at other locations such as
underarms and perineum (18). For S. aureus in these locations to eradicating,
use is made of chlorhexidine-containing soap (19). A similar scheme is used for
eradication of methicillin resistant S. aureus carriers. Within Isala are
placed annually 700 primary THA and TKA 400. If we add to this 12 hospitals it
is expected that we at least annually 6,000 prostheses can be included. To
determine the effectiveness of the eradication scheme will patients from Isala
and Rijnstate Hospital enrolled themselves cultivate prior to eradication
treatment of the pharynx, reduced both nostrils and perineum; these cultures
will be repeated in the operating room. In retrospect, the nasal carriage and
colonization of the preferred locations will be determined. In other words, it
can be established with this, or this prophylactic treatment is effective.

Definition infection
The Center for Disease Control and Prevention (CDC) classifies a surgical wound
infected when there is purulent discharge, positive cultures for
microorganisms, wound dehiscence and the presence of sign Celsius (rubor,
calor, dolor and tumor).
There are various systems score devised of which the asepsis score possible is
the best example (20). This score makes it possible to differentiate between a
minimum / superficial infection and often life-threatening deep infection (21).

The purpose of this study is to determine whether it is useful to decolonize
patients undergoing primary hip or knee replacement surgery from the S. aureus
skin bacteria.

This double-blind randomized placebo-controlled study involved two groups

Group 1: starting six days before surgery with mupirocine nasal ointment two
times each day each nostril until two days postoperatively.
This group also starts six days before surgery with Hibiscrub 4% soap solution
until the day of surgery to decolonize the axillary and perineal region.

Group 2: starting six days before surgery with placebo nasal ointment two times
each day each nostril until two days postoperatively.
This group also starts six days before surgery with placebo soap solution until
the day of surgery to decolonize the axillary and perineal region.


When we decide at the oupatient clinc to place a primary knee or hip
replacement, and informed consent is obtained. The patients enroll the study,
Then we randomize the patients in one of both groups as discribed above.
They will receive a bottle of soap and a tube of ointment with clear
instructions

Each included patient will start six days before surgery with mupirocin/placebo
nasal ointment two times each day each nostril. He or she continues the
ointment two days postoperatively.
Beside the nasal ointment they will also starts six days before surgery with
chlorhexidine/placebo soap solution to decolonize the axillary and perineal
region.. The soap is stopped at admission.

There is less risk for the participants of this study. The total duration
covers seven days in which the participant use shampoo and nasal ointment.
As described in the protocol, there are almost no side effects for the study
medication, the only thing that can occur is local skin irritation, development
of resistance is never seen in our thoracic surgery population.