A phase 2 trial of a topical antiseptic bundle in head and neck cancer surgery: Effects on surgical site infection and the oral microbiome

Abstract

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.

Keywords: Head and neck cancer surgery; Surgical site infection; Topical antisepsis.

Conflict of interest statement

Declaration of interests None.

Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.

Figures

Figure 1

Study profile.

Figure 2

Genomic mapping of the whole genomic sequence of the Eikenella sp which caused surgical site infection on to the metagenome of the pre-operative nasal cavity, pre-operative oral cavity, and post-operative oral cavity. The genome of the infectious organism closely aligns with an Eikenella sp organism identified in the pre-operative oral environment but is not found in the metagenome at the other sites. X-axis represents each gene in the Eikenella sp genome. Y-axis represents mean coverage for each gene.