The results of a randomized clinical trial support the use of piperacillin-tazobactam for reducing surgical-site infections (SSIs) following pancreatoduodenectomy, researchers reported today in JAMA.
In the pragmatic, open-label, multicenter phase 3 trial, 778 patients undergoing open pancreatoduodenectomy—a procedure to remove cancerous tumors from the head of the pancreas—were randomly assigned to receive piperacillin-tazobactam as perioperative antibiotic prophylaxis (prevention) or cefoxitin (the standard care). The primary outcome was development of postoperative SSI within 30 days. Secondary end points included 30-day mortality, development of clinically postoperative pancreatic fistula, and sepsis.
Among the 778 participants (378 in the piperacillin-tazobactam group, 400 in the cefoxitin group), the median age was 67.3, and 58.6% were men. The trial was stopped at the second interim analysis, which found that patients who received piperacillin-tazobactam had significantly fewer SSIs than those who received cefoxitin (19.8% vs 32%; absolute difference, –13.0%; 95% confidence interval [CI], –19.1% to –6.9%).
Participants treated with piperacillin-tazobactam also had lower rates of postoperative sepsis (4.2% vs 7.5%; absolute difference, −3.3%; 95% CI, −6.6% to 0.0%) and clinically relevant postoperative pancreatic fistula (12.7% vs 19.0%; absolute difference, −6.3%; 95% CI, −11.4% to −1.2%). Mortality rates at 30 days were 1.3% among participants treated with piperacillin-tazobactam and 2.5% among those receiving cefoxitin (absolute difference, −1.2%; 95% CI, −3.1% to 0.7%).
The trial investigators say the results are significant because SSIs are the most common driver of postoperative morbidity after pancreatoduodenectomy, which has remained high despite advances in surgical care.
"The effect of piperacillin-tazobactam observed in the trial was evident on stratified analyses of multiple subgroups, providing support for making broad-spectrum antibiotic prophylaxis standard care in all patients undergoing pancreatoduodenectomy," they wrote.
They added, however, that the results apply to pancreatoduodenectomy only and do not imply that broad-spectrum antibiotic prophylaxis should be used in other major operations.