Comparison of Prophylactic Intravenous Antibiotic Regimens After Endoprosthetic Reconstruction for Lower Extremity Bone Tumors
Authors: Michelle Ghert, Patricia Schneider, Victoria Giglio, Paula McKay, Andrew Duong, Nathan Evaniew, Dana Ghanem, Callum MacLeay, Kim Madden, Antonella Racano, Taryn Scott, Marilyn Swinton, Nicole Simunovic, Sheila Sprague, Diane Heels-Ansdell, Lisa Buckingham, Roberto Vélez, Alba Lopez Fernandez, Olga Sánchez-Maroto Carrizo, Mohit Bhandari, Benjamin Deheshi, Gordon Guyatt, Ginger Holt, Timothy O'Shea, R. Lor Randall, Lehana Thabane, Jay S. Wunder, Robert Turcotte, David Wilson, Peter Rose, Brian Brigman, Eleanor Pullenayegum, Peter C. Ferguson, Anthony M. Griffin, Gagan Grewal, Andrew Han, Ionna Mantas, Andrew Wylie, Krista Goulding, Nicole Andersen, Olivier Bouchereau, Firas Dandachli, Mireille Dessureault, Steven Salomon, Nathalie Ste-Marie, Ariane Lessard, Gilbert Matte, Zoe Bond, Bo Xuan Lin, Maya Biljan, Rita Chan, Deanna Cosentino, Diane Lourenco, Brittany Marriott, Gita Sobhi, Marc Isler, Sophie Mottard, Janie Barry, Hugo Saint-Yves, Marysa Bétournay, Marceline Quach, Helen Assayag, Karine Daoust, Kristine Goyette, Denis Projean, Millie Lum, Maude Bachand-Fournier, Norbert Dion, Annie Arteau, Sylvie Turmel, Anne Bertrand, Manon D'Amours, Lucie Dallaire, Nancy Gagnon, Lucie Gosselin, Gladys Grenier, Véronique Labbé, Tuong-Vi Tran, Paul Clarkson, Lisa Kondo, Baohua Wang, Judy Yip, Joel Werier, Hesham Abdelbary, Yusra Kassim, Heather Cosgrove, Kimberly Paquin, Anne-Marie Dugal, Susan Fetzer, Wendy Aikens, Shannon Puloski, Michael Monument, Kimberly Carcary, Olesja Hazenbiller, Kayla Kashluba, Jimena Rodriguez, Candice Cameron, Yee-Cheen Doung, Kenneth Gundle, James Hayden, Christopher Hart, David Jenkins, Rebecca I. Wetzel, Krista Wolf, Brooke Bernard, Sara Blefgen, Kevin Jones, John Groundland, Susie Crabtree, Jacqueline Hart, Sara Shaw, Rian Davis, Winter Redd, Susan Sorenson, Benjamin Miller, Mohammed Milhem, Jill Kain, Marian Andersen, Kathryn Hillburn, Jennifer Larson, Nancy McCurdy, Alyssa Pratt, Mary Schall, Theresa Hobbs, Kristine Johnson, Joanna Nohr, Wendi Slaughter, Jennifer Halpern, Herbert Schwartz, Julie Daniels, Eden Schafer, M. Shane Moore, John H. Healey, Kaity Chang, Linda Chen, Olivera Douvelis, Jesse Galle, Marissa Mezzancello, Yoely Tavarez, Brian Del Corral, Sabrina Lopez, Gerry O'Neill, John Abraham, Scot Brown, Meghan Angelos, Keenan Sobol, John Strony, Braden Rall, Melissa Furio, Linda Sailor, Rania Sadaka, Lauren Karel, David Geller, Bang Hoang, Janet Tingling, Clemencia Solorzano, Rosanna Wustrack, Richard O'Donnell, Melissa Zimel, Veronica Andaya, Adrianna Carrasco, Shirley Chen, Diana Ng, Yelena Koplowicz, André Spiguel, Chung Ming Chan, Charles Parker Gibbs, Mark Scarborough, MaryBeth Horodyski, Johanna Carmona, Alana Jackson, Aimee Struk, Susan Beltz, Justin C. Giaquinta, Melissa Johnson, Edward Y. Cheng, Julie Agel, Theresa Christiansen, Derek LaBar, Darlette Luke, Raffi Avedian, Linda Jordan, Deborah Kenney, Steven Chinn, Martha Hamilton, Scott Mayeda, Carol Morris, Adam Levin, Kari Albery, Jennifer Giordano, Vaishali Laljani, Anne Delisa, Nathan Mesko, Lukas Nystrom, Matthew Rerko, Heather Keaney, Rachael Yim, John Petrich, Megan E. Anderson, Mark C. Gebhardt, Benjamin Allar, Michael Greenberg, Manahil Naqvi, Ellis Prather, Emily Rademacher, Jodie Shea, James Bennett, Stacey Albuquerque, Michael Giarrusso, Albert J. Aboulafia, Matthew T. Wallace, Sally Brown, Janice Fowler, Jean Flack, Rick Battersby, Chad Taylor, David Greenberg, Sarah Dawson, Adam Riebeling, Anna Schmidt, Eric Henderson, Peter DePalo, Lisa Mack, Christine Neely-Jones, Crystallee Newton, Daniel Ressler, Holly Symonds, Iryna Gardner, Douglas Parr, Victoria Poisson, David Rozolsky, Patrick Teune, Joseph Schwab, Santiago A. Lozano-Calderon, Jonathan Baker, Emily Ann Berner, Gi Hye Im, Jason Kim, Christine Park, Rishabh Phukan, Zachary Wright, Sarah Yeates, Lalit Joshi, Timothy Damron, Tina Craig, Melissa Reale, Matthew R. DiCaprio, Bradford A. Palmer, Toni Schaeffer, Elena Cioppa, John C. Neilson, David M. King, Adam N. Wooldridge, Karen C. Gonzalez, Marie Ellestad, Kate Lewis, Tom Nelson, Nickolas Reimer, David Monson, Shervin Oskouei, Christina Lomba, Lauren Glenney, Susan Rogers, Howard Goodman, Marlena McGill, Peter Olivares, Francesca Petruccelli, Uzma Afzal, Zina Faynblat, Elizabeth Mathew, Wanda Bell-Farrell, Judith Bosley, Corilynn Hughes, Ukeme Ikiddeh-Barnes, Ashley Jones, Melissa Loomis, Alexis Solis, Christine Wade, Stephanie Friedman, Chukwuemeka N. Nzelibe, Katiri Wagner, Hina A. Jolin, Heena Patel, Joel Sorger, Nichole Leitsinger, Krista Carpenter, Denise LaGory, Steven Thorpe, Shari Lynn Nichols, Patrick Febre, Jacob Monares, Kimmai Nguyen, Nadir Sarwary, Peter Trovitch, Nicholas Bernthal, Jeffrey Eckardt, Francis Hornicek, Stephen Zoller, Gloria Kiel, Jason Madamba, Christina Shin, Adam Lindsay, Jamie Fish-Fuhrmann, Maya Culbertson, Patricia Caruso-Prendergast, Emily Garling, Richard Nicholas, Corey Montgomery, J. Aaron Holley, Rachel Jones, Melissa McAdoo, Daisy Wade, Mindy Caid, Amy Crisp, Jennifer Roberts, Tess Balach, Mark Cote, Kathleen Coyle, Kelly Rushlow, Ruth LaCasse, Daniel Lerman, Andrea Howe, Prashant Patel, Andrew Phan, Shinyi Telscher, Kurt Weiss, Mark Goodman, Alma Heyl, Chris Korenoski, Chris Ann Yeschke, Thomas Scharschmidt, Joel Mayerson, Martha Crist, Hallie Barr, Shah Alam Khan, Venkatesan Sampath Kumar, Abhinav Agarwal, Roshan Banjara, Sanjay Oli, André Mathias Baptista, Olavo Pires de Camargo, Juan Pablo Zumárraga, Juliana Freitar, Ismael Agomes, P.D. Sander Dijkstra, Michiel van de Sande, Philip Sanders, Sarah Bosma, Marieke Afra Toi, Marcos Galli Serra, Walter Parizzia, Gabriela Marinsalta, Angela Podrzaj, Mariana Foa Torres, Manuel Pérez, Lourdes Girona Brumós, Pilar Suñé, Reitze Rodseth, Leonard Marais, Luan Nieuwoudt, Chantal Rajah, Simphiwe Gumede, Andreas Leithner, Marko Bergovec, Andrea Fink, Carina Halb, Ahmed El Ghoneimy, Dina Elgalaly, Nehal Kamal, Ricardo Becker, Bruno Pereira Antunes, Carlos Roberto Galia, Julie F. Cerutti Santos, Daniel Fasolo, Mann Hong Tan, Suraya Zainul Abidin, Lai Ye Cheang, Mark Clayer, Jakub Jagiello, David Morris, Yee Chai, Steven Duong, Tran Nguyen, Peter Slobodian, Paul Jutte, Marlanka Zuur, Michelle Ghert, Patricia Schneider, Gordon Guyatt, Lehana Thabane, Roberto Vélez, Timothy O’Shea, R. Lor Randall, Robert Turcotte, David Wilson, Jay S. Wunder, André Mathias Baptista, Edward Y. Cheng, Yee-Cheen Doung, Peter C. Ferguson, Victoria Giglio, James Hayden, Diane Heels-Ansdell, Shah Alam Khan, Venkatesan Sampath Kumar, Paula McKay, Benjamin Miller, Michiel van de Sande, Juan P. Zumárraga, Mohit Bhandari
Journal: JAMA Oncology (2022)

<h3>Importance</h3> 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. <h3>Objective</h3> 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. <h3>Design, Setting, and Participants</h3> 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. <h3>Interventions</h3> 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. <h3>Main Outcomes and Measures</h3> 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. <h3>Results</h3> 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;<i>P</i> = .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;<i>P</i> = .02). Other secondary outcomes did not differ significantly between treatment groups. <h3>Conclusions and Relevance</h3> 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. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT01479283