Prevention of severe infectious complications after colorectal surgery using antimicrobial decontamination of the digestive tract

Gastrointestinal surgical procedures, including colorectal surgery, are
important therapeutic interventions. They are performed approximately 40,000
times each year in the Netherlands and surgical site infections (SSI) are
relatively frequent complications. The main consequences of SSI are a prolonged
stay (average prolongation 10-16 days) in the hospital and increased mortality
(attributable mortality 10-15%). The proposed intervention, preoperative oral
antimicrobial prophylaxis (Pre-OP), is expected to prevent half of these
complications at a low cost and with minimal adverse effects. If the
intervention is as effective as expected the estimated benefits are huge:
approximately 470 lives and ¤70 million per year, at a low cost and with hardly
any side effects.
There are only few well-designed studies supporting this strategy. In addition,
the few studies with a good design, combine oral antibiotics with mechanical
bowel preparation. The latter has been abandoned recently because there is
evidence that it is associated with a worse outcome. In conclusion, there is no
good scientific evidence supporting the use of Pre-OP. Current guidelines
consider Pre-OP in addition to perioperative intravenous antimicrobial
prophylaxis an unresolved issue, and, therefore, it is hardly applied at
present in The Netherlands.

To determine the effect of Pre-OP, in addition to perioperative intravenous
antimicrobial prophylaxis on the cumulative incidence of deep surgical site
infections (SSI) and/or mortality within 30 days after surgery in patients
undergoing elective colorectal surgery.

Double blind, randomised placebo-controlled multicentre clinical trial

Pre-OP consists of a solution (5ml) of colistin sulphate 20 mg/ml and
tobramycin 16 mg/ml. The intervention starts 3 days prior to elective surgery
and is administered four times daily for 3 consecutive days. The treatment ends
on the night before surgery. Patients in the control group will receive a
placebo solution without active ingredients, with an identical taste and
colour.

The intervention consists of non-absorbable antibiotics. When administered
orally, there is virtually no uptake of antibiotic components in the
bloodstream. It is therefore expected that the occurrence systemic side effects
is negligible. The development of antibiotic resistance might be a concern of
the use of Pre-OP. Previous studies using decontamination strategies with
comparable antimicrobial composition were unable to detect development of
antibiotic resistance, even though the duration of treatment in these studies
exceeded the timeframe of 3 days. Studies on long-term (ecological) effects of
antibiotic decontamination did not detect an increase in antibiotic resistance
either. Based on these previous studies we expect the risk of developing
antibiotic resistance to be limited.