Standard Versus Prolonged Antibiotic Prophylaxis After Pancreatoduodenectomy (SPARROW)

A clinically relevant OSI is defined by the following criteria:

• A deep surgical site infection involving any part of the abdomen (e.g. organs and/or spaces) other than the surgical incision within 90 days after surgery.
• AND Requires radiological, endoscopic or surgical intervention OR therapeutic antibiotics required for an episode of sepsis, defined as two or more SIRS criteria.
• AND Organisms isolated from an aseptically obtained culture.

An OSI is defined by the CDC definition:

o The infection appears to be related to the operative procedure and infection involves any part of the anatomy (e.g., organs or spaces) other than the incision opened or manipulated during the operative procedure, and at least one of the following is present:

• Purulent drainage from a drain that is placed into the organ/space.
• Organisms isolated from an aseptically obtained culture of fluid or tissue in the organ/space.
• An abscess or other evidence of infection involving the organ/space on direct examination, during reoperation, or by histopathologic or radiologic examination.
• Diagnosis of an organ/space SSI by a surgeon or attending physician."

Isolated OSI is defined as an OSI without concurrent anastomotic leakage (pancreatojejunostomy, hepaticojejunostomy or gastrojejunostomy). The concept of an isolated OSI is used to separately classify abdominal infections without concurrent anastomotic leakage.

A superficial surgical site infection after surgery which involves superficial or deep soft tissue (skin, muscle or fascia, but no intra-abdominal tissue), and at least one of the following criteria is present:

• Purulent drainage from the incision or subcutaneous tissue.
• Isolation of microorganisms from an aseptically obtained culture of fluid or tissue from the superficial incision of subcutaneous tissue.
• Superficial infections of the skin or subcutaneous tissue which is deliberately opened by a surgeon or attending physician OR at least one of the following signs are present: localizes pain, tenderness, swelling, heat or fever >38 degrees).

Grade B or C postoperative pancreatic fistula (POPF) defined by the International Study Group of Pancreatic Surgery definition:

Grade A: Amylase >3 times upper limit of the institutional normal serum amylase value

Grade B: Grade A + persistant drainage >3 weeks, clinically relevant change in management of POPF, percutaneous or endoscopic drainage, angiographic procedures for bleeding, or signs of infection without organ failure.

Grade C: Grade A or B requiring reoperation, resulting in organ failure or death.

Grade A, B or C defined by the ISGLS definition:

Grade A: Bile leakage requiring no or little change in patients' clinical management.

Grade B: Bile leakage requiring a change in patients clinical management (eg, additional diagnostic or interventional procedures) but manageable without relaparotomy, or a Grade A bile leakage lasting for >1 week.

Grade C: Bile leakage requiring relaparotomy

Grade A, B or C defined by the ISGPS definition:

Grade A: Early (<24h after surgery), intra- or extraluminal, clinically mild.

Grade B: Early (<24h after surgery), intra- or extraluminal and clinically severe OR later (>24h after surgery), intra- or extraluminal and clincally mild.

Grade C: Late (>24h after surgery), intra- or extraluminal and clinically severe.

Grade A, B or C defined by the ISGPS definition:

Grade A: Until day 4-7 or replacement of feeding tube > 3 days after surgery

Grade B: Until day 8-14 or replacement of feeding tube > 7 days after surgery

Grade C: >day 14 or replacement of feeding tube > 14 after surgery

Defined as a positive blood culture obtained during a septic period (defined as two or more SIRS criteria)

Defined by a positive fecal culture for Clostridium difficile

Major complications is defined by a Clavien-Dindo score of ≥III.

Clavien-Dindo classification of Surgical Complications:

Grade I: Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic and radiological interventions.

Grade II: Requiring pharmacological treatment with drugs other than such allowed for grade I complications.

Grade IIIa: Requiring surgical, endoscopic or radiological intervention not under general anesthesia Grade IIIb: Requiring surgical, endoscopic or radiological intervention under general anesthesia

Grade IVa: Life-threatening complication (including CNS complications)* requiring IC/ICU-management with single organ dysfunction (including dialysis).

Grade IVb: Life-threatening complication (including CNS complications)* requiring IC/ICU-management with multi organ dysfunction.

Grade V: Death of a patient

Reinterventions could be either radiological, surgical or endoscopic reinterventions

ICU admission

In days

Readmission into the hospital

In-hospital and 90-days mortality

Study protocol:

• Control arm: Perioperative antibiotic prophylaxis (cefazolin, metronidazole and single-dose gentamicin).
• Intervention arm: Perioperative plus prolonged antibiotics (cefuroxime and metronidazole for five postoperative days).

Rate of Antibiotic sensitivity patterns in bile cultures and cultures from surgical sites

Defined as the similarity of microorganisms between perioperative bile cultures and postoperative cultures from infectious sites.