# Comparison of Prophylactic Intravenous Antibiotic Regimens After Endoprosthetic Reconstruction for Lower Extremity Bone Tumors: A Randomized Clinical Trial

## TL;DR

A 5-day antibiotic regimen after bone tumor surgery does not reduce infection rates compared to a 1-day regimen but increases antibiotic-related complications.

## Contribution

This study provides evidence that extending postoperative antibiotic use does not improve infection prevention in complex bone tumor surgeries.

## Key findings

- The 5-day antibiotic regimen did not reduce surgical site infections compared to the 1-day regimen.
- The 5-day regimen increased antibiotic-related complications, including Clostridioides difficile–associated colitis.

## Abstract

Can a 5-day regimen of postoperative, prophylactic, intravenous antibiotics reduce the rate of surgical site infections in patients with a lower extremity bone tumor undergoing complex endoprosthetic reconstruction compared with a 1-day regimen?

In this randomized clinical trial including 604 patients in the primary analysis, the 5-day regimen did not reduce the rate of surgical site infection compared with the 1-day regimen, although it resulted in a higher rate of antibiotic-related complications, notably Clostridioides difficile–associated colitis.

The results of this study suggest that prolonging use of postoperative antibiotics beyond 1 day does not reduce the rate of surgical site infection but increases the risk of clinically significant antibiotic-related complications.

The use of perioperative, prophylactic, intravenous antibiotics is standard practice to reduce the risk of surgical site infection after oncologic resection and complex endoprosthetic reconstruction for lower extremity bone tumors. However, evidence guiding the duration of prophylactic treatment remains limited.

To assess the effect of a 5-day regimen of postoperative, prophylactic, intravenous antibiotics compared with a 1-day regimen on the rate of surgical site infections within 1 year after surgery.

This randomized clinical superiority trial was performed at 48 clinical sites in 12 countries from January 1, 2013, to October 29, 2019. The trial included patients with a primary bone tumor or a soft tissue sarcoma that had invaded the femur or tibia or oligometastatic bone disease of the femur or tibia with expected survival of at least 1 year who required surgical management by excision and endoprosthetic reconstruction. A total of 611 patients were enrolled, and 7 were excluded for ineligibility.

A 1- or 5-day regimen of postoperative prophylactic intravenous cephalosporin (cefazolin or cefuroxime) that began within 8 hours after skin closure and was administered every 8 hours thereafter. Those randomized to the 1-day regimen received identical saline doses every 8 hours for the remaining 4 days; patients, care providers, and outcomes assessors were blinded to treatment regimen.

The primary outcome in this superiority trial was a surgical site infection (superficial incisional, deep incisional, or organ space) classified according to the criteria established by the Centers for Disease Control and Prevention within 1 year after surgery. Secondary outcomes included antibiotic-related complications, unplanned additional operations, oncologic and functional outcomes, and mortality.

Of the 604 patients included in the final analysis (mean [SD] age, 41.2 [21.9] years; 361 [59.8%] male; 114 [18.9%] Asian, 43 [7.1%] Black, 34 [5.6%] Hispanic, 15 [2.5%] Indigenous, 384 [63.8%] White, and 12 [2.0%] other), 293 were randomized to a 5-day regimen and 311 to a 1-day regimen. A surgical site infection occurred in 44 patients (15.0%) allocated to the 5-day regimen and in 52 patients (16.7%) allocated to the 1-day regimen (hazard ratio, 0.93; 95% CI, 0.62-1.40; P = .73). Antibiotic-related complications occurred in 15 patients (5.1%) in the 5-day regimen and in 5 patients (1.6%) allocated to the 1-day regimen (hazard ratio, 3.24; 95% CI, 1.17-8.98; P = .02). Other secondary outcomes did not differ significantly between treatment groups.

This randomized clinical trial did not confirm the superiority of a 5-day regimen of postoperative intravenous antibiotics over a 1-day regimen in preventing surgical site infections after surgery for lower extremity bone tumors that required an endoprosthesis. The 5-day regimen group had significantly more antibiotic-related complications.

ClinicalTrials.gov Identifier: NCT01479283

This randomized clinical trial of patients with a primary bone tumor or a soft tissue sarcoma compares the effects of a 5-day vs 1-day regimen of postoperative, prophylactic, intravenous antibiotics on surgical site infections within 1 year after surgery.