This is a Phase 3 multi-center, group-randomized, crossover trial to compare nasal antimicrobial photodisinfection therapy (aPDT) with standard of care for prevention of surgical site infections in patients undergoing major elective, urgent, or emergent surgeries in a hospital setting. The main outcomes are to:

1. compare the efficacy, and
2. estimate the safety of applying nasal (aPDT) before surgery in reducing the incidence of SSIs within the initial 30 days after surgery compared to standard of care (SOC).

Participants in the intervention group will receive aPDT prior to surgery on the day of surgery.

Participants in the control group will receive standard of care surgical site prevention measures prior to surgery.

This study employs a group-randomized crossover design, comparing outcomes from the treatment group with that of a standard-of-care control group from the same hospitals. Each hospital ('site') engaged in the study will be randomly assigned to treatment plus standard-of-care or standard-of-care control on a 1:1 basis and will enroll patients into those respective groups during the first period of the study. After an approximate 6-week inactive interval period, each site will crossover to enroll the alternate group, up to a number of patients that matches the site's first period (or up to 10% more).

Eligible patients who successfully complete all screening assessments and meet inclusion and exclusion criteria will be enrolled. Patients in the treatment group will undergo aPDT treatment after admission to the preoperative area. All patients will be followed up for a 30-day post-surgery period. A patient-reported outcome (PRO) assessment to gauge the tolerability of the intervention after administration will also be performed in the treatment group.

Standard-of-care infection control practices will be applied according to infection prevention policies and procedures in place at each hospital. These practices are to remain unchanged for both groups throughout the study.

Microbiological samples will also be collected from any SSI and evaluated to establish the causative organism and its antibiotic susceptibility.

The incidence of SSIs during the 30-day postoperative period will be tracked to ensure comprehensive follow-up evaluations. In-person unscheduled visits will be conducted for medical assessment of suspected SSIs and collection of wound cultures.

Nasal Microbiota Substudy Approximately 500 study patients will have pre-treatment and post-treatment nasal swabs (in the treatment group) or single pre-surgical nasal swabs (in the control group) collected and stored. These samples will be processed for quantitative microbiological evaluation of S. aureus.

Inclusion Criteria:

1. Surgical patients, willing to sign the informed consent form and participate in the study.

2. ≥ 18 years of age

3. Presenting to an acute care hospital for major elective, urgent, or emergency surgery, defined as an open procedure involving a significant skin incision, including but not limited to the following types:

   1. Cardiac
   2. Vascular
   3. Orthopedic, including spine and 'clean' trauma
   4. Neurosurgery
   5. Breast surgeries

4. Are able to follow instructions, comply with protocol requirements, and participate in all required study visits.

Exclusion Criteria:

1. Pregnancy (current) or currently lactating. If patient is unsure of pregnancy status, a negative urine or serum pregnancy test (sensitive to 25 IU hCG) should be obtained within 14 days prior to surgery.

2. Surgical indication of infection.

3. History of surgery within 90 days prior to enrollment.

4. Anticipated surgery other than the index surgical procedure prior to patient's completion of the study.

5. Use of other nasal decolonization procedures on the day of surgery prior to the index procedure (mupirocin, povidone iodine, alcohol, etc.).

6. Patient has any medical, social or psychiatric condition(s) or current substance abuse condition that, in the opinion of the investigator, would preclude the patient's ability to provide informed consent, or to comply with the study requirements.

7. Enrollment in concomitant investigational research study in the past 30 days.

   Exclusion Criteria Specific to Treatment Group Patients Only:

8. Inability to tolerate insertion of the nasal light illuminator due to nasal obstructions or nares size, shape, or anatomical variants.

9. Known allergic reactions to components of the nasal disinfection treatment including methylene blue or chlorhexidine gluconate.