The overarching aim of this research project is to prevent orthopedic implant-associated infections. This study aims to investigate if PDT has an effect on bacterial skin colonization in order to improve skin antisepsis strategies for the prevention of surgical site infections.

Background: Periprosthetic joint infections are a feared complication after orthopedic surgery in particular in our increasing elderly population. These infections are usually difficult to treat, because microorganisms persist in biofilms on the orthopedic implant surface. Therefore, it would be desirable to prevent these infections. It is hypothesized that bacteria from the skin surface or dermis - such as Staphylococcus aureus, coagulase-negative staphylococci, or Cutibacterium sp. - are transmitted into the periimplant tissue during surgery. In an ongoing interdisciplinary study with the Orthopedic University Hospital Balgrist (data in preparation for publication), the investigators see that common skin antisepsis preparation is not effective to eliminate skin bacteria before surgery because they persist in sebaceous or sweat glands. Photodynamic therapy (PDT) has recently gained attention in the treatment of acne, a disease of the pilosebaceous unit, in which also Cutibacterium acnes is implicated. The PDT 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.

In a previous pilot study, the investigators tested if skin antisepsis is improved with previous PDT with the photosensitizer-inducing prodrug 5% topical m5-aminolevulinic acid on inguinal skin in 10 participants. The induced photosensitizer was protoporphyrin IX (Pp IX, 635 nm) activated by red light. The investigators showed a complete sterilization of colonizing skin bacteria at the same day after this treatment However, orthopedic surgeons are hesitant to perform an arthroplasty surgery after such a treatment due to skin erythema for a few days.

The investigators are entirely convinced about this novel prevention concept but need to identify the photosensitizer with the ideal balance of antibactericidal effect versus skin irritation. Building upon the data they gathered, they will explore PDT with the Protoporphyrin IX inducing prodrug photosensitizer MAL and the photosensitizer Methylene blue with potentially less local side-effects (skin erythema).

Primary outcome:

Effect of photodynamic treatment with the photosensitizers Pp IX (5-ALA) and Methylene blue in combination with surgical antisepsis on bacterial skin colonization on the day of application and on day 1, 3, and 5 after PDT.

Secondary outcome:

Effect of PDT on the skin microbiome using molecular techniques.

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 PDT 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 PDT
• Participants who had a history of photosensitivity disorder
• Fitzpatrick's skin phototype V-VI

30 days