Rethinking Perioperative Antibiotic Prophylaxis for Low-Risk Head and Neck Procedures.

OBJECTIVE: For true clean-contaminated head and neck procedures, the literature supports ≤24 hours of perioperative antibiotics. However, there are certain otolaryngology procedures with low surgical site infection (SSI) risk for which there is negligible benefit from antibiotic prophylaxis. The objective of this evaluation was to describe antibiotic use and adherence to evidence-based institutional guidelines in low-risk head and neck procedures. METHODS: This was a single-center, retrospective cohort study of patients undergoing low-risk clean-contaminated head and neck procedures wherein antibiotic prophylaxis was not indicated, based on evidence-based institutional guidelines. RESULTS: Among the 291 included patients, perioperative antibiotics were unnecessarily administered in 29% of patients. Among patients who received antibiotics, 76% received preoperative antibiotics and 41% received postoperative antibiotics, for a median duration of 7 days. There were no significant differences in SSIs, mortality, and length of stay for those receiving perioperative antibiotics versus those not receiving perioperative antibiotics. CONCLUSION: These data highlight the need for antibiotic stewardship interventions and partnerships between antibiotic stewardship teams and surgical services.

Helenalin Analogues Targeting NF-κB p65: Thiol Reactivity and Cellular Potency Studies of Varied Electrophiles.

Helenalin is a pseudoguaianolide natural product that targets Cys38 within the DNA binding domain of NF-κB transcription factor p65 (RelA). Helenalin contains two Michael acceptors that covalently modify cysteines: a α-methylene-γ-butyrolactone and a cyclopentenone. We recently reported two simplified helenalin analogues that mimic the biological activity of helenalin and contain both electrophilic moieties. To determine the individual contributions of the Michael acceptors toward NF-κB inhibition, we synthesized a small library of helenalin-based analogues containing various combinations of α-methylene-γ-butyrolactones and cyclopentenones. The kinetics of thiol addition to a subset of the analogues was measured to determine the relative thiol reactivities of the embedded electrophiles. Additionally, the cellular NF-κB inhibitory activities of the analogues were determined to elucidate the contributions of each Michael acceptor to biological potency. Our studies suggest the α-methylene-γ-butyrolactone contributes most significantly to the NF-κB inhibition of our simplified helenalin analogues.