Prospective Randomized Clinical Trial on Oral and Intravenous Antibiotic Prophylaxis in Colorectal Surgery.
Prospective Randomized Clinical Trial on Oral and Intravenous Antibiotic Prophylaxis in Colorectal Surgery.
Elective colon surgery is considered a clean-contaminated procedure, with a Surgical Site
 Infection (SSI) rate not inferior to 10%. For many years the role of Mechanical Bowel
 Preparation (MBP) has been universally recognized as an effective measure to reduce colonic
 bacterial load and consequently SSI rate, mostly in European Countries. However, in the early
 1970s has been demonstrated a further SSI risk reduction in colon surgery if oral
 non-absorbable antibiotics were added to MBP and for the next 30 years this became the
 standard of care prior to elective colon surgery, especially in the US. Nowadays,
 Meta-analyses have demonstrated that MBP does not impact upon postoperative morbidity or
 mortality, and as such it should not be prescribed routinely. Conversely, recent evidence has
 suggested that there may be a role for combined MBP and oral antibiotics, or oral antibiotics
 alone in the prevention of surgical site infection (SSI).

 The aim of this trial is to evaluate the efficacy of preoperative oral antibiotics
 prophylaxis for preventing surgical site infections in elective colorectal surgery.
This study is a Multicenter, Prospective, Randomized, Controlled Trial on preoperative oral
 antibiotics prophylaxis in colorectal surgery.

 INCLUSION & EXCLUSION CRITERIA:

 All consecutive patients undergoing elective colorectal resection should be included in the
 trial.

 Exclusion criteria:

 -  Emergency procedures

 -  Appendicectomy (unless procedure involves a right hemicolectomy)

 -  Primarily urological/gynecological or vascular procedure - e.g. ileal conduit,
 Hartmann's during ovarian surgery, resection during abdominal aortic aneurysm repair.

 -  Diagnostic laparotomy/laparoscopy without intestinal resection.

 -  Surgery involving multi-visceral surgery - e.g. pelvic exenteratio

 -  Controindication for mechanical preparation

 -  Allergy to used drugs

 -  Patients who refuse to participate in the study

 -  Patients with intra-abdominal sepsis before surgery (abscess).

 -  Patients who received antibiotics for any reason within two weeks prior to surgery.

 -  Patients who do not comply strictly with the assigned prophylaxis regimen.

 -  Patients who cannot be followed at least 4 weeks after surgery.

 Patients recruitment:

 Consecutive eligible patients will be recruited at the outpatient clinic in the participating
 center by the involved physician (surgeon). All patients fulfilling the inclusion criteria
 will be informed about the study by the physician. After consent is given, central data
 acquisition will take place web-based and patients will be randomized in 2 groups and treated
 according to the study protocol. Patients unable or refusing to provide informed consent will
 be treated according to current clinical practice.

 Primary Outcome:

 - Incidence of surgical site infections (superficial or deep)

 Secondary Outcomes:

 -  Perioperative complication

 -  Anastomotic dehiscence

 -  Post-operative ileus

 -  Extra-abdominal complications

 -  Readmission

 -  Reoperation

 -  Length of hospital stay

 -  Mortality

 -  Adverse effects of antibiotics (diarrhea, C. difficile infection)

 Covariates:

 In addition to demographic, procedure and outcome data, the following data will be collected
 as confounding variables to permit accurate risk adjustment of outcomes.

 -  The American Society of Anesthesiologists (ASA) score

 -  Cardiovascular and metabolic co-morbidities (includes chronic obstructive pulmonary
 disease (COPD), chronic kidney disease (CKD), peripheral vascular disease (PVD) and
 diabetes mellitus)

 -  History of previous abdominal surgery

 -  Preoperative administration of immunosuppressive/steroid therapy

 -  Preoperative Chemo-RadioTherapy

 -  Preoperative Albumin Serum Level (g/dL)

 Follow-up:

 -  Patients will be followed for 30 days after surgery. All secondary outcome measures will
 be recorded if they occurred at any point from post-operative day 0 (day of surgery) to
 Day 30.

 -  No change to normal follow-up should take place.

 -  The follow-up of patients includes a clinical evaluation 30 days after surgical
 intervention supported by blood analysis (WBC count and CRP), to completely exclude the
 presence of any infectious complication. Presence of fever and/or WBC count/CRP
 elevation will require further investigation with radiological imaging and will be
 considered an infectious post operative complication (SSI or not).

 PROJECT TIMELINE:

 Data collection will take place in two years. Follow-up data will also be collected for up to
 30 days after surgery.

 Data Collection and Governance:

 Data will be collected and stored online. Communication between the clients and the Server
 where is hosted the online platform is secured under TLS protocol with an encryption
 certificate SHA256 with RSA 2048 bits (e 65537). In order to maximize the data protection,
 the physical HD where is sored the database is encrypted too. Access to the online platform
 will be possible only previous Login. Each device logged in will be identified and the user
 will be able to ban the access from a specific device. Each physician will be able to see and
 modify only the data of patients added from his center. The online platform will check the
 validity and the correct format of the fields and will generate an excel table to import to
 the statistic software.

 Intervention strategies:

 Patients will be randomized to intravenous antibiotic prophylaxis alone or oral antibiotics
 prepara-tion in association with intravenous antibiotic prophylaxis.

 In the group of patients not treated with oral antibiotics standard intravenous prophylaxis
 will be administered at the time of induction of anesthesia, redosing with prolonged surgery:
 amoxicil-lin/clavulanic acid 2000/200 mg or, in the event of allergy to penicillin,
 clindamycin 600 mg + gen-tamycin 2 mg/kg. In case of Chronic Renal Failure dose adjustment
 will be necessary in presence of Creatinine Clearance respectively <30 ml/min and <60 ml/min
 in accordance to pharmacologic recommendations.

 In the other group oral prophylaxis consists of Bimixin (Neomicin + Bacitracin tablet) 25000
 UI + 2500 UI). In the postoperative period no more doses will be administered because the
 drug is not absorbed by gastrointestinal mucosa and its progression from the stomach to the
 colon is slowed down by post-operative ileus. In this group of patient standard intravenous
 antibiotic prophylaxis will be administered at induction of anesthesia.

 Any mechanical bowel preparation will be administered, as indicated by each center. Surgeon,
 anesthesiologist and nurse will know if patient had assumed oral antibiotics and intrave-nous
 antibiotics or intravenous prophylaxis alone. Data concerning SSI rate, infectious
 complica-tion other than SSI and not infectious complications will be collected during
 hospital stay. 30 days after the operation blood tests (WBC, CRP) and clinical evaluation
 will confirm the absence of any infectious complication.
Inclusion criteria:

 -  Summary: All consecutive patients undergoing colorectal resection should be included.

 -  Age: Age 18 years or above.

 -  The general health condition of the patient permits general anesthesia (ASA-
 classification I-III).

 -  Absence of allergy to the oral antibiotics employed

 -  Timing: Elective procedures.

 -  Technique: Open, laparoscopic, laparoscopic-assisted or laparoscopic converted to
 open.

 -  Returns to theatre: Each patient should only be included in the study once. Return to
 theatre during the same admission or follow up should be collected as a complication.

 -  Included procedures: Any colorectal resection (See Appendix B).

 -  Mechanical Bowel Preparation: Any mechanical bowel preparation (as indicated by each
 centre).

 Exclusion criteria:

 -  Emergency procedures

 -  Appendicectomy (unless procedure involves a right hemicolectomy)

 -  Primarily urological/gynecological or vascular procedure - e.g. ileal conduit,
 Hartmann's during ovarian surgery, resection during abdominal aortic aneurysm repair.

 -  Diagnostic laparotomy/laparoscopy without intestinal resection.

 -  Surgery involving multi-visceral surgery - e.g. pelvic exenteratio

 -  Controindication for mechanical preparation

 -  Allergy to used drugs (neomycin sulfate, amoxicillin-clavulanic acid)

 -  Patients who refuse to participate in the study

 -  Patients with intra-abdominal sepsis before surgery (abscess).

 -  Patients who received antibiotics for any reason within two weeks prior to surgery.

 -  Patients who do not comply strictly with the assigned prophylaxis regimen.

 -  Patients who cannot be followed at least 4 weeks after surgery.