title: Timing of surgical antimicrobial prophylaxis: a phase 3 randomised controlled trial.
abstract: Based on observational studies, administration of surgical antimicrobial prophylaxis (SAP) for the prevention of surgical site infection (SSI) is recommended within 60 min before incision. However, the precise optimum timing is unknown. This trial compared early versus late administration of SAP before surgery.
  
  
  
  In this phase 3 randomised controlled superiority trial, we included general surgery adult inpatients (age ≥18 years) at two Swiss hospitals in Basel and Aarau. Patients were randomised centrally and stratified by hospital according to a pre-existing computer-generated list in a 1:1 ratio to receive SAP early in the anaesthesia room or late in the operating room. Patients and the outcome assessment team were blinded to group assignment. SAP consisted of single-shot, intravenous infusion of 1·5 g of cefuroxime, a commonly used cephalosporin with a short half-life, over 2-5 min (combined with 500 mg metronidazole in colorectal surgery). The primary endpoint was the occurrence of SSI within 30 days of surgery. The main analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT01790529.
  
  
  
  Between Feb 21, 2013, and Aug 3, 2015, 5580 patients were randomly assigned to receive SAP early (2798 patients) or late (2782 patients). 5175 patients (2589 in the early group and 2586 in the late group) were analysed. Median administration time was 42 min before incision in the early group (IQR 30-55) and 16 min before incision in the late group (IQR 10-25). Inpatient follow-up rate was 100% (5175 of 5175 patients); outpatient 30-day follow-up rate was 88·8% (4596 of 5175), with an overall SSI rate of 5·1% (234 of 4596). Early administration of SAP did not significantly reduce the risk of SSI compared with late administration (odds ratio 0·93, 95% CI 0·72-1·21, p=0·601).
  
  
  
  Our findings do not support any narrowing of the 60-min window for the administration of a cephalosporin with a short half-life, thereby obviating the need for increasingly challenging SAP timing recommendations.
  
  
  
  Swiss National Science Foundation, Hospital of Aarau, University of Basel, Gottfried und Julia Bangerter-Rhyner Foundation, Hippocrate Foundation, and Nora van Meeuwen-Häfliger Foundation.
authors.affiliation: Department of General Surgery, University Hospital Basel, Basel, Switzerland; University of Basel, Basel, Switzerland. Electronic address: walter.weber@usb.ch.
authors.forename: Walter P
authors.initials: WP
authors.lastname: Weber
authors.affiliation: Department of General Surgery, University Hospital Basel, Basel, Switzerland; University of Basel, Basel, Switzerland.
authors.forename: Edin
authors.initials: E
authors.lastname: Mujagic
authors.affiliation: Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
authors.forename: Marcel
authors.initials: M
authors.lastname: Zwahlen
authors.affiliation: Department of General Surgery, Hospital of Aarau, Aarau, Switzerland.
authors.forename: Marcel
authors.initials: M
authors.lastname: Bundi
authors.affiliation: Department of General Surgery, University Hospital Basel, Basel, Switzerland; University of Basel, Basel, Switzerland.
authors.forename: Henry
authors.initials: H
authors.lastname: Hoffmann
authors.affiliation: Department of General Surgery, University Hospital Basel, Basel, Switzerland; University of Basel, Basel, Switzerland.
authors.forename: Savas D
authors.initials: SD
authors.lastname: Soysal
authors.affiliation: Department of General Surgery, University Hospital Basel, Basel, Switzerland; University of Basel, Basel, Switzerland.
authors.forename: Marko
authors.initials: M
authors.lastname: Kraljević
authors.affiliation: Department of General Surgery, University Hospital Basel, Basel, Switzerland; University of Basel, Basel, Switzerland.
authors.forename: Tarik
authors.initials: T
authors.lastname: Delko
authors.affiliation: Department of General Surgery, University Hospital Basel, Basel, Switzerland; University of Basel, Basel, Switzerland; Department of General Surgery, Hospital of Aarau, Aarau, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: von Strauss
authors.affiliation: Department of General Surgery, University Hospital Basel, Basel, Switzerland; University of Basel, Basel, Switzerland.
authors.forename: Lukas
authors.initials: L
authors.lastname: Iselin
authors.affiliation: Department of General Surgery, Hospital of Aarau, Aarau, Switzerland.
authors.forename: Richard X Sousa
authors.initials: RXS
authors.lastname: Da Silva
authors.affiliation: Department of General Surgery, University Hospital Basel, Basel, Switzerland; University of Basel, Basel, Switzerland.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Zeindler
authors.affiliation: University of Basel, Basel, Switzerland.
authors.forename: Rachel
authors.initials: R
authors.lastname: Rosenthal
authors.affiliation: Department of General Surgery, University Hospital Basel, Basel, Switzerland; University of Basel, Basel, Switzerland.
authors.forename: Heidi
authors.initials: H
authors.lastname: Misteli
authors.affiliation: Department of Anaesthesiology, Hospital of Aarau, Aarau, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kindler
authors.affiliation: Department of Anaesthesiology, Hospital of Aarau, Aarau, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Müller
authors.affiliation: University of Basel, Basel, Switzerland; Department of Clinical Research, University Hospital Basel, Basel, Switzerland.
authors.forename: Ramon
authors.initials: R
authors.lastname: Saccilotto
authors.affiliation: University of Basel, Basel, Switzerland; Department of Anaesthesiology, University Hospital Basel, Basel, Switzerland.
authors.forename: Andrea Kopp
authors.initials: AK
authors.lastname: Lugli
authors.affiliation: University of Basel, Basel, Switzerland; Department of Anaesthesiology, University Hospital Basel, Basel, Switzerland.
authors.forename: Mark
authors.initials: M
authors.lastname: Kaufmann
authors.affiliation: Department of General Surgery, University Hospital Basel, Basel, Switzerland; University of Basel, Basel, Switzerland.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Gürke
authors.affiliation: Department of General Surgery, University Hospital Basel, Basel, Switzerland; University of Basel, Basel, Switzerland; Indiana University School of Medicine South Bend, Goshen Center for Cancer Care, Goshen, IN, USA; Harper Cancer Research Institute, South Bend, IN, USA.
authors.forename: Urs
authors.initials: U
authors.lastname: von Holzen
authors.affiliation: Department of General Surgery, University Hospital Basel, Basel, Switzerland; University of Basel, Basel, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Oertli
authors.affiliation: Department of Infectious Diseases, Hospital of Aarau, Aarau, Switzerland.
authors.forename: Evelin
authors.initials: E
authors.lastname: Bucheli-Laffer
authors.affiliation: Department of General Surgery, University Hospital Basel, Basel, Switzerland; University of Basel, Basel, Switzerland.
authors.forename: Julia
authors.initials: J
authors.lastname: Landin
authors.affiliation: University of Basel, Basel, Switzerland; Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
authors.forename: Andreas F
authors.initials: AF
authors.lastname: Widmer
authors.affiliation: Department of Infectious Diseases, Hospital of Aarau, Aarau, Switzerland.
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Fux
authors.affiliation: Department of General Surgery, Hospital of Aarau, Aarau, Switzerland.
authors.forename: Walter R
authors.initials: WR
authors.lastname: Marti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000890:Anti-Infective Agents / Q000627:therapeutic use; D002444:Cefuroxime / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000627:therapeutic use; D008875:Middle Aged; D012307:Risk Factors; D013530:Surgical Wound Infection / Q000188:drug therapy* / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D008795:Metronidazole; D002444:Cefuroxime