The overarching aim of this research project is to prevent orthopedic implant-associated infections. This study aims to investigate if photodynamic therapy has an effect on bacterial skin colonization and decrease number of colonizing bacteria associated with sebaceous and sweat glands in order to improve skin antisepsis strategies for the prevention of surgical site infections.

Background. Periprosthetic joint infections are increasing due to our elderly population with the need of a joint prosthesis. These infections are difficult to treat, because bacteria are able to be sessile (biologically inactive) in the biofilms formed within one day on the orthopedic implant surface. Notably, the current available antibiotics do not penetrate the biofilm or are not active against the sessile form of bacteria - rifampicin being the only antibiotic being active. Therefore, prevention is key. In the current paradigm, bacteria from the skin surface or dermis - such as Staphylococcus aureus, coagulase-negative staphylococci, or Cutibacterium sp. - contaminate the peri-implant tissue during surgery. In an ongoing study with the Orthopedic University Hospital Balgrist (manuscript in preparation), the investigators found that the common practice of skin antisepsis is ineffective to eliminate skin bacteria before surgery. Strikingly, the skin bacteria hide in sebaceous or sweat glands. Photodynamic treatment has recently gained attention in the treatment of acne patients, a disease of the pilosebaceous unit, in which also Cutibacterium acnes is implicated. The photodynamic treatment works here on the one hand through a long-lasting destruction of the sebaceous glands, and on the other hand due to anti-inflammatory and antimicrobial effects.

Hypothesis. The investigators hypothesize that photodynamic treatment improves skin antisepsis before surgical implantation of foreign material by reduction of persistent skin colonizing bacteria through the destruction of the sebaceous and sweat glands and by its bactericidal effects Overall and specific objectives. The overarching aim of this research project is to prevent orthopedic implant-associated infections. The specific aim is to evaluate the effect of photodynamic treatment on colonizing bacteria immediately after surgical skin antisepsis (aim 1) and 3 weeks later (aim 2). In aim 3, the investigators will evaluate phylogenetic similarity of same bacterial species before and after photodynamic treatment if they persist.

Methods. The investigators will collect scrapings from the skin surface and quantitatively evaluate bacterial species and density before and after photodynamic treatment in combination with skin antisepsis of povidone-iodine/alcohol, in aim 1 immediately after skin antisepsis, and in aim 2, 21 days after photodynamic treatment. For aim 2, the investigators will additionally evaluate changes of sebaceous and sweat glands after photodynamic treatment using histopathology. To evaluate phylogenetic similarity of same bacterial species before and after photodynamic treatment, the investigators will investigate the core genome using whole genome sequencing.

Relevance and outlook. The current study will investigate if photodynamic treatment is able to improve preoperative skin preparation to decrease surgical site infections in hip arthroplasty surgery. A decrease of implant-associated infections has multiple benefits, among others reduced morbidity, mortality and lower health costs. This study shall provide the fundament for a prospective cohort study of patients with planned hip arthroplasty for investigating the effect of photodynamic treatment before skin antisepsis.

Inclusion Criteria:

Healthy male and female participants ≥ 18 years who

• volunteer for the pilot study in which a routine photodynamic treatment in the Department of Dermatology will be applied and effect of skin colonization will be analyzed, and
• an informed consent is signed by the participant (after information about the project).

Exclusion Criteria:

• Pregnant and lacting women
• Participants with inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc.,
• Participants taking antibiotics in the 14 days prior to the photodynamic treatment or until follow-up at 21 days
• Participants who received oral retinoid therapy within the last 6 months
• Participants who received anti-inflammatory agents as NSAR within the 14 days prior and after the PDT
• Participants taking any photosensitizing drugs within 4 weeks prior to the photodynamic treatment (PDT)
• Participants who had a history of photosensitivity disorder
• Fitzpatrick's skin phototype V-VI

from baseline until follow up on day 21