麻豆传媒

BALTIMORE -- There was no benefit with a longer- versus shorter-duration prophylactic antibiotic regimen in reducing surgical site infections after endoprosthetic reconstruction for lower-extremity bone tumors, the randomized showed.

In the multinational study of over 600 patients, surgical site infections occurred in 15.0% of patients given a 5-day course of intravenous cephalosporins, as compared with 16.7% of those allocated to a 24-hour course (HR 0.93, 95% CI 0.62-1.40), reported Michelle Ghert, MD, of McMaster University in Hamilton, Ontario.

There was, however, a significantly higher risk of clinically serious antibiotic-related complications for the longer-duration group (5.1% vs 1.6% in the 24-hour group; HR 3.24, 95% CI 1.17-8.98).

"So, when you are writing your post-op orders, consider the uncertainty of the benefits and the relative confidence in the harm," she said in a presentation at the hybrid Musculoskeletal Tumor Society (MSTS) annual meeting, held virtually and in-person.

"Is this going to change practice? I think there's a potential for that," Ghert told 麻豆传媒. "It will be up to individual surgeons. We will prescribe antibiotics because we don't want infections. But are we doing it the right way? We'll have to balance the benefit and the harm, and I think people will be doing more of that."

The rationale for the PARITY (Prophylactic Antibiotic Regimens in Tumor Surgery) trial was the wide variation in clinical practice regarding the duration of IV antibiotic administration following surgery, she explained. For example, a her team published in 2012 prior to the start of PARITY showed that 33.7% of surgeons felt that antibiotics should be discontinued after 24 hours, while 41.4% said they should be administered until the suction drain is removed.

"A deep surgical site infection is devastating, not only for the patient but for the surgeon as well," said Ghert.

The aim of PARITY, therefore, was to determine whether 5 days of postoperative antibiotic administration would reduce surgical site infections compared with a 24-hour regimen after endoprosthetic reconstruction of the femur or tibia.

The trial was conducted across 48 sites in 12 countries from January 2013 to October 2019. Ghert noted that a central adjudication committee (CAC) was tasked with identifying cases of surgical site infections. A total of 604 patients were included: 311 were randomized to receive IV cephalosporin postoperatively for 24 hours plus 4 days of placebo, and 293 were randomized to receive IV cephalosporin for 5 days.

Across both arms, 96 patients (15.9%) had at least one surgical site infection within 1 year of limb salvage surgery. "This is a very high number, but the CAC adjudicated these, and I have 100% confidence in this number," Ghert said.

In addition, 20 patients (7%) had at least one antibiotic-related complication that required either hospitalization or some kind of medical intervention. Clostridioides difficile-associated colitis and diarrhea were the most common antibiotic-related complications observed.

C. difficile-associated colitis and diarrhea are clearly related to the use of antibiotics, Ghert said, adding that she suspected that 5 days of antibiotic treatment resulted in patients' microbiome "taking a huge hit," making them more susceptible to these complications.

PARITY also found the following:

• About 25% of all patients had at least one unplanned operation within a year of surgery, with no difference between groups

• The most common types of re-operations were irrigation and debridement, implant exchange, and implant revision

• 30% of all patients had at least one oncologic event within a year, with no difference between groups

• The mortality rate was 13% within 1 year, with no difference between groups

One key limitation, noted Ghert, was that "diagnosing surgical site infection is not as easy as it sounds," although the problem was offset by the rigor of the adjudication process, she said.

The broader impact of PARITY -- which Ghert pointed out was the first international multicenter randomized controlled trial in bone cancer surgery -- is that it demonstrates that randomized trials in orthopedic oncology can be conducted.

"If the PARITY trial has clinical impact, it will be the first time that our society as a whole in orthopedic oncology has been able to do something that really has the data and rigorous study design where you can walk away and say this data is real, and I can use it in my practice," she said.

"What I took away [from PARITY] was that the incidence of infection in megaprosthesis surgery is really, really high at over 16%," said MTMS session moderator Kurt Weiss, MD, of the University of Pittsburgh Medical Center. "That's a huge number."

While there does not seem to be an advantage to longer courses of antibiotics vis-a-vis infection, there definitely were deleterious effects of prolonged antibiotics in terms of antibiotic side effects," Weiss told 麻豆传媒. "The finding that we can do real harm with longer antibiotic courses is very important."

Weiss agreed with Ghert that, from a big-picture perspective, the trial offers results with significant statistical power. "With PARITY, my colleagues and I can really trust the findings because they are so robust," he said. "We don’t get that a lot, and never have we gotten it from a prospective, randomized clinical trial."

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