Gut Decolonisation With Neomycin/Metronidazole or Rifaximin Before Colon Surgery

Surgical site infections (SSIs) are the most frequent infections in patients undergoing colon surgery, leading to considerable morbidity, mortality and increased healthcare costs. As SSIs are often caused by endogenous gut flora, oral antibiotic gut decolonisation prior to colon surgeries is standard practice. However the optimal antibiotic regimen remains unclear.

This phase IV, multicenter, open-label randomized controlled trial aims to evaluate whether a rifaximin-based protocol is non-inferior to the current standard regimen of neomycin and metronidazole in preventing SSIs.

Rifaximin is a semi-synthetic derivate with poor systemic absorption, allowing for local gut action and a broad antibacterial spectrum covering gram-positiv, - negativ, aerobic aswell as anaerobic bacteria. It is approved in Switzerland for hepatic encephalopathy and has a favorable safety profile with mostly mild gastrointestinal side effects. Neomycin is FDA-approved for preoperative gut decolonisation. Common side effects include nausea, vomiting and diarrhea.

The study will include about 458 patients undergoing planned colon surgery at five swiss hospitals. Patients will be randomized in 1:1 ratio to receive either rifaximin 2x550mg per day or Neomycin 2x500mg plus Metronidazol 2x500mg per day, administeres orally at 10:00 AM and 10:00 PM on the day before surgery. Mechanical bowel preparation, when applied, is scheduled between 4:00 PM and 08:00 PM on the same day. The primary outcome is the incidence of SSI. Secondary outcomes include mortality and length of hospital stay.

Ramdomization is computer-generated. Blinding is limited to the responsible statisticians. Clinicians and patients are aware of the assigned treatment. Safety assessments focus on known side effects as documentes by reculatory agencies.

The study adresses a clinically important gap in evidence for the best antibiotic regimen for preoperative gut decolonisation.

• Rifaximin (Xifaxan) (Drug): Preoperative gut decolonization protocol based on oral Rifaximin 2x550mg 10 am and 10 pm on the day preceding the surgery
• Metronidazole (Drug): Preoperative gut decolonization protocols based on oral Neomycine 2x500mg and Metronidazole 2x500mg 10 am and 10pm on the day preceding the surgery
• Neomycin Sulfate (Drug): Preoperative gut decolonization protocols based on oral Neomycine 2x500mg and Metronidazole 2x500mg 10 am and 10pm on the day preceding the surgery

Primary outcomes

• Surgical Site Infection (deep and/or organ space) [The occurrence of surgical site infections is evaluated at two time points: 1. At time of dismissal from the hospital (up to d30) 2. If the patients is discharged: Via post-discharge surveillance at 30 days after surgery]: Assessment of surgical site infection (SSI) is following Swissnoso standard procedures and comprises a routine surveillance for means of quality control in all participating centers, irrespective of participation in this study. In brief, IP nurses supervised by infectious diseases specialists or other physicians without hierarchical link with the departments of surgery are in charge of the surveillance in each participating hospital. Patients are followed-up by IP nurses during their hospital stay and post-discharge for 30 days. Any suspicion of SSI or unclear situation is presented to the supervising physician for decision about the diagnosis of SSI. The post-discharge follow-up is done performed by IP nurses through standardized phone interviews with the patients. CDC critiera will be applied to determine the presence of SSI.

Secondary outcomes

• Mortality [up to 30 days after surgery]: To investigate the occurance of death
• Length of stay [up to 30 days after surgery]: Time of hospitalization after surgery

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* aged ≥ 18 years
* undergoind planned colon surgery
* colon surgery will be included in Swissnoso SSI surveillance
* informed consent

Exclusion Criteria:

* contraindications and/or intolerance to one of the study compounds
* patients with underlying active infection (wound contamination class IV) at the timepoint of incision
* pregnant women
* unable to follow study protocol

NIH grants: 2025