Journal article
Piperacillin-Tazobactam Compared With Cefoxitin as Antimicrobial Prophylaxis for Pancreatoduodenectomy: A Randomized Clinical Trial
JAMA : the journal of the American Medical Association, Vol.329(18), pp.1579-1588
2023
DOI: 10.1001/jama.2023.5728
PMCID: PMC10119777
PMID: 37078771
Abstract
Despite improvements in perioperative mortality, the incidence of postoperative surgical site infection (SSI) remains high after pancreatoduodenectomy. The effect of broad-spectrum antimicrobial surgical prophylaxis in reducing SSI is poorly understood.
To define the effect of broad-spectrum perioperative antimicrobial prophylaxis on postoperative SSI incidence compared with standard care antibiotics.
Pragmatic, open-label, multicenter, randomized phase 3 clinical trial at 26 hospitals across the US and Canada. Participants were enrolled between November 2017 and August 2021, with follow-up through December 2021. Adults undergoing open pancreatoduodenectomy for any indication were eligible. Individuals were excluded if they had allergies to study medications, active infections, chronic steroid use, significant kidney dysfunction, or were pregnant or breastfeeding. Participants were block randomized in a 1:1 ratio and stratified by the presence of a preoperative biliary stent. Participants, investigators, and statisticians analyzing trial data were unblinded to treatment assignment.
The intervention group received piperacillin-tazobactam (3.375 or 4 g intravenously) as perioperative antimicrobial prophylaxis, while the control group received cefoxitin (2 g intravenously; standard care).
The primary outcome was development of postoperative SSI within 30 days. Secondary end points included 30-day mortality, development of clinically relevant postoperative pancreatic fistula, and sepsis. All data were collected as part of the American College of Surgeons National Surgical Quality Improvement Program.
The trial was terminated at an interim analysis on the basis of a predefined stopping rule. Of 778 participants (378 in the piperacillin-tazobactam group [median age, 66.8 y; 233 {61.6%} men] and 400 in the cefoxitin group [median age, 68.0 y; 223 {55.8%} men]), the percentage with SSI at 30 days was lower in the perioperative piperacillin-tazobactam vs cefoxitin group (19.8% vs 32.8%; absolute difference, -13.0% [95% CI, -19.1% to -6.9%]; P < .001). Participants treated with piperacillin-tazobactam, vs cefoxitin, had lower rates of postoperative sepsis (4.2% vs 7.5%; difference, -3.3% [95% CI, -6.6% to 0.0%]; P = .02) and clinically relevant postoperative pancreatic fistula (12.7% vs 19.0%; difference, -6.3% [95% CI, -11.4% to -1.2%]; P = .03). Mortality rates at 30 days were 1.3% (5/378) among participants treated with piperacillin-tazobactam and 2.5% (10/400) among those receiving cefoxitin (difference, -1.2% [95% CI, -3.1% to 0.7%]; P = .32).
In participants undergoing open pancreatoduodenectomy, use of piperacillin-tazobactam as perioperative prophylaxis reduced postoperative SSI, pancreatic fistula, and multiple downstream sequelae of SSI. The findings support the use of piperacillin-tazobactam as standard care for open pancreatoduodenectomy.
ClinicalTrials.gov Identifier: NCT03269994.
Details
- Title: Subtitle
- Piperacillin-Tazobactam Compared With Cefoxitin as Antimicrobial Prophylaxis for Pancreatoduodenectomy: A Randomized Clinical Trial
- Creators
- Michael I D'Angelica - Memorial Sloan Kettering Cancer CenterRyan J Ellis - American College of SurgeonsJason B Liu - Brigham and Women's HospitalBrian C Brajcich - American College of SurgeonsMithat Gönen - Memorial Sloan Kettering Cancer CenterVanessa M Thompson - American College of SurgeonsMark E Cohen - American College of SurgeonsSusan K Seo - Memorial Sloan Kettering Cancer CenterEmily C Zabor - Memorial Sloan Kettering Cancer CenterMichele L Babicky - The Oregon Clinic/Providence Portland Medical Center, PortlandDavid J Bentrem - Northwestern UniversityStephen W Behrman - New England Baptist HospitalKimberly A Bertens - University of OttawaScott A Celinski - Baylor University Medical CenterCarlos H F Chan - University of IowaMary Dillhoff - The Ohio State UniversityMatthew E B Dixon - Rush University Medical CenterCarlos Fernandez-Del Castillo - Massachusetts General HospitalSepideh Gholami - University of California, DavisMichael G House - Indiana University HealthPaul J Karanicolas - University of TorontoHarish Lavu - Thomas Jefferson UniversityShishir K Maithel - Emory University HospitalJohn C McAuliffe - Montefiore Medical CenterMark J Ott - Intermountain HealthcareBradley N Reames - University of Nebraska Medical CenterDominic E Sanford - Washington University School of Medicine, St Louis, MissouriUmut Sarpel - Mount Sinai Medical CenterCourtney L Scaife - Huntsman Cancer InstitutePablo E Serrano - McMaster UniversityTravis Smith - Gunderson Health System, La Crosse, WisconsinRebecca A Snyder - The University of Texas MD Anderson Cancer CenterMark S Talamonti - NorthShore University Health, Evanston, IllinoisSharon M Weber - University of Wisconsin–MadisonAdam C Yopp - The University of Texas Southwestern Medical CenterHenry A Pitt - Rutgers, The State University of New JerseyClifford Y Ko - VA Greater Los Angeles Healthcare System
- Resource Type
- Journal article
- Publication Details
- JAMA : the journal of the American Medical Association, Vol.329(18), pp.1579-1588
- DOI
- 10.1001/jama.2023.5728
- PMID
- 37078771
- PMCID
- PMC10119777
- ISSN
- 0098-7484
- eISSN
- 1538-3598
- Language
- English
- Electronic publication date
- 04/20/2023
- Date published
- 2023
- Academic Unit
- Surgery; Radiation Oncology
- Record Identifier
- 9984398211002771
Metrics
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