A phase 2 trial of a topical antiseptic bundle in head and neck cancer surgery: Effects on surgical site infection and the oral microbiome
Joseph Zenga,
Samantha Atkinson,
Tina Yen,
Becky Massey,
Michael Stadler,
Jennifer Bruening,
William Peppard,
Michael Reuben,
Michael Hayward,
Brian Mesich,
Blake Buchan,
Nathan Ledeboer,
Joyce L. Sanchez,
Raphael Fraser,
Chien-Wei Lin,
Mary L. Holtz,
Musaddiq Awan,
Stuart J. Wong,
Sidharth V. Puram,
Nita Salzman
Affiliations
Joseph Zenga
Department of Otolaryngology, Division of Head and Neck Surgical Oncology and Reconstruction, Medical College of Wisconsin, Milwaukee, WI, United States; Corresponding author at: Division Chief, Don and Sharyn Blatnik Professor of Head and Neck Surgical Oncology and Reconstruction, Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, 9200 W. Wisconsin Ave. Milwaukee, WI 53226, United States.
Samantha Atkinson
Center for Microbiome Research, Medical College of Wisconsin, Milwaukee, WI, United States; Department of Microbiology & Immunology, Medical College of Wisconsin, Milwaukee, WI, United States
Tina Yen
Department of Surgery, Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, United States
Becky Massey
Department of Otolaryngology, Division of Head and Neck Surgical Oncology and Reconstruction, Medical College of Wisconsin, Milwaukee, WI, United States
Michael Stadler
Department of Otolaryngology, Division of Head and Neck Surgical Oncology and Reconstruction, Medical College of Wisconsin, Milwaukee, WI, United States
Jennifer Bruening
Department of Otolaryngology, Division of Head and Neck Surgical Oncology and Reconstruction, Medical College of Wisconsin, Milwaukee, WI, United States
William Peppard
Department of Surgery, Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, United States; Department of Pharmacy, Medical College of Wisconsin, Milwaukee, WI, United States
Michael Reuben
Department of Pharmacy, Children's Wisconsin, Milwaukee, WI, United States
Michael Hayward
Center for Microbiome Research, Medical College of Wisconsin, Milwaukee, WI, United States; Department of Pediatrics, Division of Gastroenterology, Medical College of Wisconsin, Milwaukee, WI, United States; Children's Research Institute, Children's Wisconsin, Milwaukee, WI, United States
Brian Mesich
Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, United States
Blake Buchan
Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, United States
Nathan Ledeboer
Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, United States
Joyce L. Sanchez
Department of Medicine, Division of Infectious Diseases, Medical College of Wisconsin, Milwaukee, WI, United States
Raphael Fraser
Department of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, United States
Chien-Wei Lin
Department of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, United States
Mary L. Holtz
Center for Microbiome Research, Medical College of Wisconsin, Milwaukee, WI, United States; Department of Pediatrics, Division of Gastroenterology, Medical College of Wisconsin, Milwaukee, WI, United States; Children's Research Institute, Children's Wisconsin, Milwaukee, WI, United States
Musaddiq Awan
Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, United States
Stuart J. Wong
Department of Medicine, Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, United States
Sidharth V. Puram
Department of Otolaryngology, Division of Head and Neck Surgical Oncology and Reconstruction, Washington University School of Medicine, Saint Louis, MO, United States
Nita Salzman
Center for Microbiome Research, Medical College of Wisconsin, Milwaukee, WI, United States; Department of Pediatrics, Division of Gastroenterology, Medical College of Wisconsin, Milwaukee, WI, United States; Children's Research Institute, Children's Wisconsin, Milwaukee, WI, United States
Summary: Background: Head and neck cancer (HNC) surgery remains an important component of management but is associated with a high rate of surgical site infection (SSI). We aimed to assess the safety and efficacy of a topical mucosal antiseptic bundle in preventing SSI and evaluate microbial predictors of infection through a genomic sequencing approach. Methods: This study was an open-label, single-arm, single-center, phase 2 trial of a topical mucosal antiseptic bundle in patients with HNC undergoing aerodigestive tract resection and reconstruction. Patients underwent topical preparation of the oral mucosa with povidone-iodine (PI) and chlorhexidine gluconate (CHG) pre- and intra-operatively followed by oral tetracycline ointment every 6 hours for 2 days post-operatively. The primary outcome was change in bacterial bioburden at the oral surgical site. Secondary outcomes included safety, SSI, and microbial predictors of infection. Findings: Of 27 patients screened between January 8, 2021, and May 14, 2021, 26 were enrolled and 25 completed the study. There were no antiseptic-related adverse events. The topical mucosal antiseptic bundle significantly decreased oral bacterial colony-forming units from pre-operative levels (log10 mean difference 4·03, 95%CI 3·13–4·;92). There were three SSI (12%) within 30 days. In correlative genomic studies, a distinct set of amplicon sequence variants in the post-operative microbiome was associated with SSI. Further, despite no instance of post-operative orocervical fistula, metagenomic sequence mapping revealed the oral cavity as the origin of the infectious organism in two of the three SSI. Interpretation: The bacterial strains which subsequently caused SSI were frequently identified in the pre-operative oral cavity. Accordingly, a topical antiseptic bundle decreased oral bacterial bioburden throughout the peri-operative period and was associated with a low rate of SSI, supporting further study of topical antisepsis in HNC surgery. Funding: Alliance Oncology.
