Effects of Photodynamic Therapy on the Human Inguinal Skin Microbiome to Improve Antiseptic Effect - a Pilot Study
Phase: NA
Conditions: Postoperative Wound Infection Deep Incisional Surgical Site, Prosthesis and Implants, Surgical Site Infection, Prosthetic Joint Infection
Sponsor: University of Zurich

PHOMIC, Version 4.0, 14.01.2020 
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Clinical Study Protocol 
EFFECTS OF PHOTODYNAMIC THERAPY ON THE HUMAN INGUINAL SKIN MICROBIOME TO 
IMPROVE ANTISEPTIC EFFECT 
SHORT TITLE: Effect of photodynamic treatment on skin microbiome (PHOMIC) 
Single center study 
Study Type: 
Health-related intervention  
Study Categorization: 
Other Clinical Trial Category A 
Study Registration: 
Bundesamtes für Gesundheit: www.kofam.ch. 
SNCTP000003386 
International trial registry ClinicalTrials.gov 
(clinicaltrials.gov) NCT04067843 
Study Identifier: 
SNCTP000003386 
Sponsor study Identifier: PHOMIC 
Sponsor-Investigator and 
Principal Investigator: 
PD Dr. med. Yvonne Achermann 
University Zurich 
Division of Infectious Diseases and Hospital Hygiene 
Yvonne Achermann, MD 
University Hospital Zurich 
Rämistrasse 100, 8091 Zürich 
Switzerland  
Phone: 044 255 34 02 
E-Mail: yvonne.achermann@usz.ch
Study Intervention: 
Effects of photodynamic treatment on skin microbiome 
Protocol Version and Date: 
V04, 14.1.2020 
CONFIDENTIAL 
The information contained in this document is confidential and the property of the Division of 
Infectious Diseases of the University Hospital Zurich. The information may not - in full or in part - be 
transmitted, reproduced, published, or disclosed to others than the applicable Independent Ethics 
Committee(s) and Competent Authority(ies) without prior written authorization from Division of 
Infectious Diseases of the University Hospital except to the extent necessary to obtain informed 
consent from those participants who will participate in the study. 

 
 
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SIGNATURE PAGE 
Study number 
 
SNCTP000003386 
Bundesamtes für Gesundheit: www.kofam.ch. 
International 
trial 
registry 
ClinicalTrials.gov 
(clinicaltrials.gov): NCT04067843 
 
Study Title 
Effects of photodynamic therapy on the human 
inguinal skin microbiome to improve antiseptic 
effect  
 
 
Sponsor-Investigator (Principal Investigator): 
 
This clinical trial protocol was subject to critical review and has been approved by the Sponsor-
Investigator. The information herein is consistent with 
- 
the current risk/benefit evaluation of the intervention, 
- 
the moral, ethical and scientific principles governing clinical research as set out in the  
  current version of the Declaration of Helsinki, Good Clinical Practice.  
 
 
PD Dr. med. Yvonne Achermann 
 
Zürich, 14.1.2020 
Place/Date 
 
Signature 
 
 
 
 

 
 
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TABLE OF CONTENTS 
SIGNATURE PAGE ...............................................................................................................2 
STUDY SYNOPSIS ................................................................................................................6 
LIST OF ABBREVIATIONS ....................................................................................................9 
1 
INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE ............................ 10 
1.1 
Sponsor, Sponsor-Investigator (Principal Investigator) ....................................... 10 
1.2 
Investigator for Intervention: Photodynamic treatment ........................................ 10 
1.3 
Study design and statistician (Biometrician) ....................................................... 10 
1.4 
Study Nurse ....................................................................................................... 10 
1.5 
Laboratory .......................................................................................................... 10 
1.6 
Monitoring Institution .......................................................................................... 11 
ETHICAL AND REGULATOR ASPECTS ............................................................................. 11 
1.7 
Study Registration .............................................................................................. 11 
1.8 
Categorization of the Study ................................................................................ 11 
1.9 
Competent Ethics Committee (CEC) .................................................................. 11 
1.10 Ethical Conduct of the Study .............................................................................. 12 
1.11 Declaration of Interest ........................................................................................ 12 
1.12 Participant Information and Informed Consent ................................................... 12 
1.13 Participant Privacy and Confidentiality ............................................................... 12 
1.14 Early Termination of the Study ........................................................................... 13 
1.15 Protocol Amendments ........................................................................................ 13 
2 
INTRODUCTION ......................................................................................................... 13 
2.1 
Background and Rationale ................................................................................. 13 
2.2 
Study Intervention and Indication ....................................................................... 14 
2.3 
Clinical Evidence to Date ................................................................................... 15 
2.4 
Justification of Study Intervention ....................................................................... 15 
2.5 
Explanation for Choice of Comparator Intervention ............................................ 15 
2.6 
Risk / Benefits .................................................................................................... 15 
2.7 
Study Population ................................................................................................ 16 
3 
STUDY OBJECTIVES ................................................................................................. 17 
3.1 
Overall Objective ................................................................................................ 17 
3.2 
Primary Objective ............................................................................................... 17 
3.3 
Secondary Objectives ........................................................................................ 17 
3.4 
Safety Objectives ............................................................................................... 17 
4 
STUDY OUTCOMES .................................................................................................. 18 
4.1 
Primary Outcome ............................................................................................... 18 
4.2 
Secondary Outcomes ......................................................................................... 18 
4.3 
Safety Outcomes ................................................................................................ 18 
5 
STUDY DESIGN AND COURSE OF STUDY .............................................................. 19 
5.1 
General Study Design and Justification of the Design ........................................ 19 
5.2 
Study Duration and Study Schedule ................................................................... 19 
5.3 
Methods of Minimizing Bias ................................................................................ 21 
6 
STUDY POPULATION ................................................................................................ 21 
6.1 
Eligibility Criteria ................................................................................................. 21 

 
 
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6.1.1 Inclusion Criteria ..................................................................................... 21 
6.1.2 Exclusion Criteria .................................................................................... 21 
6.2 
Recruitment and Screening ................................................................................ 22 
6.3 
Criteria for Withdrawal/ Discontinuation of Participants ...................................... 22 
7 
STUDY INTERVENTION............................................................................................. 23 
7.1 
General Information ........................................................................................... 23 
7.1.1 Study Intervention ................................................................................... 23 
7.1.2 Control Intervention ................................................................................ 23 
7.2 
Administration of Study Intervention ................................................................... 23 
7.2.1 Study Intervention ................................................................................... 23 
7.2.2 Modification of Interventions ................................................................... 23 
7.3 
Compliance with Intervention ............................................................................. 24 
7.4 
Data Collection and Follow-up for Withdrawn Participants ................................. 24 
7.5 
Concomitant Intervention(s) ............................................................................... 24 
8 
STUDY PROCEDURES .............................................................................................. 24 
8.1 
Study Flow Chart/Table of Study Procedures and Assessments ........................ 24 
8.2 
Assessments of Outcomes ................................................................................. 26 
8.2.1 Assessment of Primary Outcome ............................................................ 26 
8.2.2 Assessment of Secondary Outcomes ..................................................... 27 
8.2.3 Assessment of Safety Outcomes ............................................................ 27 
8.2.4 Assessments in Participants who prematurely Stop the Study ................ 27 
8.3 
Procedures at Each Visit .................................................................................... 27 
8.3.1 Screening Visit = Visit 1 .......................................................................... 27 
8.3.2 Visit 2 = Day 1 of the study ..................................................................... 28 
8.3.3 Visit 3 (day 21±7) .................................................................................... 28 
8.3.4 Visit 4 = End of Study Visit (day 35±7) .................................................... 29 
9 
SAFETY ...................................................................................................................... 29 
9.1 
Definitions .......................................................................................................... 29 
9.2 
Recording and Assessment of Serious Adverse Events ..................................... 30 
9.3 
Reporting of Serious Adverse Events ................................................................. 30 
9.4 
Follow up of (Serious) Adverse Events ............................................................... 31 
10 
STATISTICAL METHODS ........................................................................................... 31 
10.1 Hypothesis ......................................................................................................... 31 
10.2 Determination of Sample Size ............................................................................ 31 
10.3 Planned Analyses .............................................................................................. 31 
10.3.1 Datasets to be Analyzed, Analysis Populations ....................................... 31 
10.3.2 Primary Analysis ..................................................................................... 31 
10.3.3 Secondary Analyses ............................................................................... 32 
10.3.4 Interim Analyses ..................................................................................... 32 
10.3.5 Safety Analysis ....................................................................................... 32 
10.3.6 Deviation(s) from the Original Statistical Plan ......................................... 32 
10.4 Handling of Missing Data and Drop-Outs ........................................................... 32 
11 
ELIGIBILITY OF THE PROJECT SITE(S) ................................................................... 32 
12 
DATA QUALITY ASSURANCE AND CONTROL ......................................................... 32 
12.1 DATA HANDLING AND RECORD KEEPING ..................................................... 33 

 
 
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12.1.1 Case Report Forms ................................................................................ 33 
12.1.2 Specification of Source Documents ........................................................ 33 
12.1.3 Record Keeping / Archiving..................................................................... 34 
12.2 Data Management .............................................................................................. 34 
12.3 Routine Monitoring ............................................................................................. 35 
12.4 Audits and Inspections ....................................................................................... 35 
12.5 Confidentiality, Data Protection .......................................................................... 35 
12.6 Storage of Biological Material and Related Health Data ..................................... 35 
13 
PUBLICATION AND DISSEMINATION POLICY ......................................................... 36 
14 
FUNDING AND SUPPORT ......................................................................................... 36 
14.1 Funding .............................................................................................................. 36 
14.2 Other Support .................................................................................................... 36 
15 
INSURANCE ............................................................................................................... 36 
16 
REFERENCES ............................................................................................................ 38 
17 
APPENDICES ............................................................................................................. 39 
 
 
 

 
 
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STUDY SYNOPSIS 
Sponsor 
/ 
Sponsor-
Investigator 
PD Dr. med. Yvonne Achermann 
Study Title: 
Effects of photodynamic therapy on the human inguinal 
skin microbiome to improve antiseptic Effect – a pilot 
study 
Short Title / Study ID: 
Effects of photodynamic treatment on skin microbiome 
(PHOMIC) 
Protocol Version and Date: 
v04, 14.1.2020   
Trial registration: 
Bundesamtes 
für 
Gesundheit: 
www.kofam.ch. 
SNCTP000003386 
International trial registry ClinicalTrials.gov (clinicaltrials.gov) 
NCT04067843 
Study 
category 
and 
Rationale 
Other clinical study Category A 
Background and Rationale: 
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 a 
ongoing interdisciplinary study with the Orthopedic University 
Hospital Balgrist (data in preparation for publication), we see 
that common skin antisepsis preparation is not effective to 
eliminate skin bacteria before surgery because they persist in 
sebaceous or sweat glands. Photodynamic treatment (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. 
Objective(s): 
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. 

 
 
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Outcome(s): 
Primary outcome 
1. Immediate 
effect 
of 
photodynamic 
treatment 
in 
combination with surgical antisepsis on bacterial skin 
colonization 
1.1. To quantitatively evaluate bacterial density and 
species before photodynamic treatment and after 
photodynamic 
treatment 
and 
antisepsis 
skin 
preparation 
2. Long-term effect on bacterial skin colonization in the 
groin after photodynamic treatment 
2.1. To quantitatively evaluate bacterial density and 
species before and after photodynamic treatment (7 
and 21 days) 
2.2. To evaluate changes of sebaceous and sweat glands 
after photodynamic treatment on skin biopsies 
Secondary outcome 
3. To evaluate phylogenetic similarity of  the microbiota 
on the dermis before and three weeks following  
photodynamic treatment  
 
Study design: 
Pilotstudy, open label, single center 
Inclusion / Exclusion criteria: 
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 
Study Intervention:  
 
Photosensitizer application, followed by fluorescence 
photography and photodynamic therapy (PHT) (1x) over 
15 minutes at the dermatology ward 
 
Skin swabs 
 
Skin biopsies in only 5 participants  

 
 
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Reference Intervention: 
From a current prospective study at the University Hospital 
Balgrist, we have the reference database of colonizing 
bacteria in the groin without photodynamic treatment. In 
addition, we will take skin swabs before and after skin 
antisepsis without antisepsis in 10 participants. 
Number of Participants with 
Rationale: 
Aim: 20 volunteers  
There will be only descriptive statistics to see if numbers of 
colonizing bacteria are decreased with photodynamic 
treatment to plan a clinical trial in patients getting a hip joint 
arthroplasty and previous antisepsis. 
Study Duration: 
1 year 
Study Schedule: 
 
Project start (FPFV): July 2019  
o First participant: July 2019 
o Last participant: June 2020 
 
Project end (LPLV): July 2020 
Investigator(s): 
Yvonne Achermann, MD 
Division of Infectious Diseases and Hospital Hygiene 
University Hospital Zurich 
Rämistrasse 100, 8091 Zürich 
Email: yvonne.achermann@usz.ch 
Tel: 044 255 34 02 
 
Dr. med Laurence Imhof 
Department of Dermatology University Hospital of Zurich, 
Zurich 
University Hospital Zurich 
Rämistrasse 100, 8091 Zürich 
Email: laurence.imhof@usz.ch 
Tel:+41 44 255 36 11 
 
Study Centre(s): 
Single-center  
Statistical Considerations: 
Categorical data will be tested for differences using Fisher’s 
exact or chi-squared tests, as appropriate, whereas 
continuous variables will be tested using Wilcoxon rank sum 
tests. 
GCP Statement: 
This study will be conducted in compliance with the protocol, 
the current version of the Declaration of Helsinki, the ICH-GCP 
as well as all national legal and regulatory requirements.  
 

 
 
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LIST OF ABBREVIATIONS 
AE 
Adverse Event  
ClinO 
Clinical Trial Ordinance (KlinV) 
CRF 
Case Report Form  
eCRF 
Electronic Case Report Form  
GCP 
Good Clinical Practice  
ICH 
International Council on Harmonization 
ISF 
Investigator Site File  
PI 
Principal Investigator  
SAE 
Serious Adverse Event  
SDV 
Source Data Verification  
SNCTP 
Swiss National Clinical Trial Portal 
SOP 
Standard Operating Procedure 
TMF 
Trial Master File  
PJI 
C. avidum 
CNS 
Sp. 
CEC 
PDT 
MAL 
NSAR 
Periprosthetic Joint Infection 
Cutibacterium avidum 
Cogulase-negative staphylococci 
Species 
Competent Ethics Committee  
Photodynamic therapy 
Methyl aminolevulinate 
Non-steroidal anti-inflammatory drugs 

1 INVESTIGATORS 
AND 
STUDY 
ADMINISTRATIVE 
STRUCTURE  
1.1 Sponsor, Sponsor-Investigator (Principal Investigator) 
Division of Infectious Diseases and Hospital Hygiene 
PD Dr. med. Yvonne Achermann 
University Hospital Zurich 
Rämistrasse 100, 8091 Zürich 
Tel: 044 255 34 02 
Email: yvonne.achermann@usz.ch 
1.2 Investigator for Intervention: Photodynamic treatment 
Department of Dermatology University Hospital of Zurich, Zurich 
Dr. med Laurence Imhof 
University Hospital Zurich 
Rämistrasse 100, 8091 Zürich 
Tel:+41 44 255 36 11 
Email: laurence.imhof@usz.ch 
 
1.3 Study design and statistician (Biometrician) 
Division of Infectious Diseases and Hospital Epidemiology 
PD Dr. med. Stefan Kuster 
University Hospital Zurich 
Rämistrasse 100, 8091 Zürich 
Tel: +41 44 255 43 10  
Email: stefan.kuster@usz.ch 
1.4 Study Nurse 
Division of Infectious Diseases and Hospital Epidemiology 
Daniela Egli 
University Hospital Zurich 
Tel +41 43 25 30 686 
daniela.egli@usz.ch 
1.5 Laboratory 
Institute of Medical Microbiology 
Prof. Dr. med. Reinhard Zbinden 
University Zurich 

 
 
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Gloriastrasse 30/32, 8006 Zürich 
Tel. +41 44 634 27 00 
Email: rzbinden@imm.uzh.ch 
 
1.6 Monitoring Institution 
Since we only measure microbiological data from skin samples, we think, that an interne 
monitoring would be adequate. See chapter 12.3.  
ETHICAL AND REGULATOR ASPECTS 
Before this study will be conducted, the protocol, the proposed participant information and consent 
form as well as other study-specific documents will be submitted to a properly constituted 
Competent Ethics Committee (CEC) in agreement with local legal requirements, for formal 
approval.  
The decision of the CEC concerning the conduct of the study will be made in writing to the 
Sponsor-Investigator before commencement of this study. The clinical study can only begin once 
approval from the CEC has been received. 
1.7 Study Registration 
The study will be registered in the Swiss Federal Complementary Database („Portal“) (Registry 
of ongoing Research Projects (RoPS)) and in the international trial registry ClinicalTrials.gov 
(clinicaltrials.gov). 
1.8 Categorization of the Study 
Category A: The health-related study intervention (PTD, taking biopsies) entails only minimal 
risks and burdens. 
1.9 Competent Ethics Committee (CEC)  
Approval from the appropriate constituted Competent Ethics Committee is sought for the clinical 
trial. The reporting duties and allowed time frame are respected. No substantial amendments 
are made to the protocol without prior CEC approval, except where necessary to eliminate 
apparent immediate hazards to study participants.Premature study end or interruption of the 
study is reported within 15 days. The regular end of the study is reported to the CEC within 90 
days, the final study report shall be submitted within one year after study end. Amendments are 
reported according to chapter 2.9. 

 
 
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1.10 Ethical Conduct of the Study 
The study will be carried out in accordance with principles enunciated in the current version of the 
Declaration of Helsinki, the guidelines of Good Clinical Practice (GCP) issued by ICH, and Swiss 
competent authority’s requirements.  
CEC will receive annual safety and interim reports and be informed about non-substantial 
amendments, the course of the study, and the study stop/ end in agreement with local 
requirements. 
1.11 Declaration of Interest  
No conflict of interest 
1.12 Participant Information and Informed Consent 
The investigator must explain to each Participant the nature of the study, its purpose, the 
procedures involved, the expected duration, the potential risks and benefits and any discomfort it 
may entail. Each participant must be informed that the participation in the study is voluntary and 
that he/she may withdraw from the study at any time and that withdrawal of consent will not affect 
his/her subsequent medical treatment.  
The participant must be informed that his/her medical records may be examined by authorized 
individuals other than their treating physician. 
All participants for this study will be provided a participant information sheet and a consent form 
describing this study and providing sufficient information for participants to make an informed 
decision about their participation in this study.   
The participant information sheet and the consent form will be submitted with the protocol for 
review and approval for the study by the CEC. The formal consent of a participant, using the 
approved consent form, must be obtained before that participant is submitted to any study 
procedure.   
The participant should read and consider the statement before signing and dating the informed 
consent form, and should be given a copy of the signed document. The consent form must also 
be signed and dated by the investigator (or his designee) and it will be retained as part of the 
study records. 
1.13 Participant Privacy and Confidentiality 
The investigators are liable to treat the entire information related to the study and the compiled 
data strictly confidentially. Any passing-on of information to persons that are not directly involved 
in the study must be approved by the owner of the information.  
Data generation, transmission, archiving and analysis of personal data within this study, strictly 
follows the current Swiss legal requirements for data protection. Prerequisite is the voluntary 
approval of the Participant given by signing the informed consent prior start of participation of the 
clinical trial.  
Individual participant medical information obtained as a result of this study is considered 
confidential and disclosure to third parties is prohibited. Participant’s confidentiality will be further 
ensured by utilizing participant identification code numbers to correspond to treatment data in the 
computer files. 

 
 
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Such medical information may be given to the participant’s personal physician or to other 
appropriate medical personnel responsible for the participant’s welfare, if the patient has given 
his/her written consent to do so. 
Data generated as a result of this study are to be available for inspection on request by the 
monitors and by the CEC. 
1.14 Early Termination of the Study  
The Sponsor-Investigator may discontinue the study prematurely according to certain 
circumstances: 
 
ethical concerns, 
 
insufficient participant recruitment, 
 
when the safety of the participants is doubtful or at risk, respectively, 
 
alterations in accepted clinical practice that make the continuation of a clinical trial unwise,  
 
early evidence of benefit or harm of the experimental intervention  
1.15 Protocol Amendments 
Substantial amendments (significant changes) are only implemented after approval of the CEC. 
 
Significant changes to be authorized by the CEC are the following: 
 
 
changes affecting the participants’ safety and health, or their rights and obligations;  
 
changes to the protocol, and in particular changes based on new scientific knowledge 
which concern the trial design, the method of investigation, the endpoints or the form of 
statistical analysis; 
 
a change of trial site, or conducting the clinical trial at an additional site; or 
 
a change of sponsor, coordinating investigator or investigator responsible at a trial site. 
 
Under emergency circumstances, deviations from the protocol to protect the rights, safety and 
well-being of human participants may proceed without prior approval of the sponsor and the CEC. 
Such deviations shall be documented and reported to the sponsor and the CEC as soon as 
possible. 
All Non-substantial amendments are communicated to the CEC within the Annual Safety Report 
(ASR). 
2 INTRODUCTION 
2.1 Background and Rationale 
The use of orthopedic implants has been steadily increasing over the last 50 years. Despite 
considerable technical progress, including perioperative skin disinfection and antibiotic 
prophylaxis, implant-associated infections remain a feared complication. Infection rates up to 2% 
after primary joint arthroplasties (Tande and Patel 2014) have been described. National data 
published by Swissnoso – the National Center for Infection Prevention –reported an infection rate 
of 1.2% in hip arthroplasties (Vergleichsbericht 2015/2016). Considering an infection rate of up to 
1.2%, 400 surgeries with primary hip arthroplasty implantation at the Orthopedic Department of 

 
 
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the Balgrist University Hospital (data of 2015) would result in five periprosthetic joint infections 
(PJI) per year, which is medically highly relevant regarding morbidity, mortality and estimated 
costs of 225’000 CHF in total.  
Because bacteria grow and persist in biofilms on the implant surface such infections are difficult 
to eradicate. Definite cure of biofilm infections requires adequate surgical debridement and 
prolonged treatment with an antimicrobial agent resulting in high health-care costs (Tande and 
Patel 2014). Most commonly isolated microorganisms in implant-associated infections are 
staphylococci, streptococci, enterococci, Gram-negative bacteria, and anaerobic bacteria such 
as Cutibacterium acnes/avidum (formerly Propionibacterium acnes/avidum) (Tande and Patel 
2014). 
The majority of implant-associated infections are acquired during surgery. It is hypothesized that 
the same bacteria that colonize the skin surface contaminate the orthopedic implant and cause 
acute or chronic infections (Pulido, Ghanem et al. 2008). Prevention of implant-associated 
infections is key to avoid re-operations and prolonged antibiotic treatment. Current preoperative 
prevention strategies are multifaceted with the focus on skin antisepsis and single shot of an 
antibiotic within 30-60 minutes before surgery (Bratzler, Dellinger et al. 2013, Dumville, McFarlane 
et al. 2015). Preoperative skin disinfection is performed with alcoholic povidone-iodine (PVI) or 
chlorhexidine gluconate (CHG) prior to implantation as a standard skin preparation (Dumville, 
McFarlane et al. 2013, Berrios-Torres, Umscheid et al. 2017). Povidone iodine oxidizes cell 
constituents and inactivates proteins by iodinating them. Regarding the skin commensal 
Cutibacterium acnes, it could be shown that despite administration of standard preoperative 
prophylaxis before shoulder arthroplasty surgeries, C. acnes could be detected in different sample 
types (in dermis, fascia, synovium, and glenoid tissue of shoulder) of 3 out of 10 patients without 
any signs of infection (Matsen, Russ et al. 2015). There is an increasing number of studies 
reporting the presence of bacteria in deep tissue, which is commonly considered as sterile. A 
recent study by Lee et al. found viable C. acnes in the dermal tissue in seven out of 10 male 
volunteers after surface skin antisepsis (Lee, Pottinger et al. 2014). All these study results have 
led to the assumption that not only the superficial skin bacteria but also bacteria in the dermis 
may find the way to deeper structures and infect an implant.  
We hypothesize that local photodynamic treatment (PDT) is able to reduce persistent skin 
colonizing bacteria through the destruction of the sebaceous and sweat glands as well through 
bactericidal effects and thus improve skin antisepsis before surgical incision and implantation of 
foreign material leading to a lower rate of surgical site infections. The aim of this pilotstudy in 
maximum 20 participants within a year is to evaluate the effect of PDT on colonizing bacteria 
immediately before surgical skin antisepsis and after it (1 and 3 weeks later). If we see promising 
results in this pilotstudy, we will plan a prospective clinical trial in patients undergoing hip 
arthroplasty surgery.  
2.2 Study Intervention and Indication 
Study invervention 
Indication 
PDT 
- 
Bactericidal effect on skin bacteria 
- 
Destruction of sebaceous and sweat glands 
Skin swabs 
- 
To measure bacterial growth of colonizing 
bacteria 
Skin biopsies in 5 participants 
- 
To measure growth of persistent bacteria in 

 
 
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sebaceous and sweat glands (Microbiology) 
- 
To analyze skin/dermis structure including size 
of 
sebaceous 
and 
sweat 
glands 
(dermatohistopathology) 
2.3 Clinical Evidence to Date  
Photodynamic treatment (PDT) has recently gained attention in the treatment of acne, a disease 
of the pilosebaceous unit, in which also C. acnes is implicated. The PDT works here on the one 
hand through a longlasting destruction of the sebaceous glands, and on the other hand due to 
anti-inflammatory and antimicrobial effects (Sakamoto, Lopes et al. 2010). In following studies, 
photodynamic therapy not only validated its efficient activity against bacteria involved in acne 
such as C. acnes, it showed also activity against various other classes of microorganisms (Awad, 
Tovmasyan et al. 2016). The mechanism of action of the PDT is a photochemical reaction through 
the generation of reactive oxygen species in the presence of oxygen, mainly excited singlet 
oxygen, by a non-toxic-photosensitizer reacting with visible light. Photodynamic treatment is 
routinely performed among others for non-melanoma skin cancer and therapy-refractory 
inflammatory dermatoses at the Department of Dermatology at the University Hospital Zurich. 
The treatment enjoys great popularity as it is well tolerated, can be repeated arbitrarily often, and 
gives excellent cosmetic results.  
2.4 Justification of Study Intervention 
Skin swabs and small skin biopsies have only minimal risks and the PDT enjoys great popularity 
as it is well tolerated. Therefore, we select this promising treatment to investigate an innovative 
strategy to improve skin antisepsis in a pilotstudy. If we see that we have sterile cultures after 
PDT and skin antisepsis we will plan a larger prospective study based on these data. 
2.5 Explanation for Choice of Comparator Intervention 
Not applicable, study without PDT is currently ongoing (study acronym DESCAV, ethical number 
2018-00783) at the Orthopedic University Hospital Balgrist. The results of this prospective study 
will be used as reference for this pilot study results. 
2.6 Risk / Benefits  
In the following, we describe benefits, weakness, opportunities, and risks of this study.  

 
 
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Possible side effects of the PDT treatment are pain during PDT in the area of treatment, erythema 
and edema during and after light treatment (Borgia, Giuffrida et al. 2018). These side effects are 
self-limiting.  
Since our study interventions (see above) have minimal risks for participants, it is reasonable to 
conduct this pilotstudy before starting a larger clinical trial with patients undergoing hip 
arthroplasty surgery. 
2.7 Study Population  
Twenty healthy male and female volunteers’ ≥ 18 years will be recruited for this clinical study. 
The study will be approved by the local ethical committee and conducted with a study nurse 
(Daniela Egli) and a doctoral thesis student (Isabel Waldmann) in collaboration with the Clinic 
for Dermatology at the University Hospital Zurich, with the Institute of Medical Microbiology at 
the University of Zurich, and with the Orthopedic University Hospital Balgrist in Zurich. An 
informed consent will be obtained from each participant. We will exclude pregnant and lactating 
women, 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 within the 14 days prior and after the 
photodynamic treatment, participants taking any photosensitizing drugs within 4 weeks prior to 
the photodynamic treatment, participants who had a history of photosensitivity disorder or having 
a fitzpatrick’s skin phototype V-V (16) 
We will not include vulnerable participants  
 
Benefits
• Important topic in our society of more elderly patients 
with the increasing need of orthopedic implants
• Photodynamic treatment is a promising method for 
improving skin anti-sepsis..
• established network with infectious diseases 
specialists (Lead), microbiologists, dermatologists, 
and orthopedic surgeons
Weakness
Opportunities
• Improved skin antisepsis by photdynamic treatment 
would change routine praxis in orthopedic surgery as 
well as overall in surgery with the consequent 
reduction in morbidity, mortality, and health-care 
costs
Risks
• Minimal risk (transient erythema and pain) using 
PDT (no long-term sequelae)

 
 
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3 STUDY OBJECTIVES  
3.1 Overall Objective 
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 before surgical skin antisepsis (aim 1) and 3 weeks later (aim 2). In 
addition in aim 3, we will evaluate phylogenetic similarity of same bacterial species before and 
after photodynamic treatment if they persist. 
3.2 Primary Objective 
Here we use skin swabs from the groin before and after Photodynamic treatment. For all these 
swabs, we will use the scratching method using a scalpel as already applied in a previous study 
(ethical approval BASEC-Nr 2016-01017). The skin swabs will be sent to the microbiology 
laboratory of the University of Zurich for bacterial analysis.  
We distinguish between an immediate (day 0) and long-term effect (3 weeks) investigating the 
skin microbiome after PDT.  
In Detail:  
1. Immediate effect of photodynamic treatment in combination with surgical antisepsis on 
bacterial skin colonization 
1.1. To quantitatively evaluate bacterial density and species before photodynamic treatment 
and after photodynamic treatment and antisepsis skin preparation  
1.1.1. Parameter: growth of bacteria (yes/no), number and identification of bacteria 
(species name), semiquantitative amount of bacteria 
2. Long-term effect on bacterial skin colonization in the groin after photodynamic treatment 
2.1. To quantitatively evaluate bacterial density and species before and after 7 and 21 days 
of photodynamic treatment  
2.1.1. Parameter: growth of bacteria (yes/no), number and identification of bacteria 
(species name), semiquantitative amount of bacteria 
2.2. To evaluate changes of sebaceous and sweat glands after photodynamic treatment on 
skin biopsies 
2.3. Parameters: Number and size of glands 
3.3 Secondary Objectives 
To evaluate phylogenetic similarity of the microbiota on the dermis before and one and three 
weeks following photodynamic treatment  
3.4 Safety Objectives 
Evaluation of adverse events 

 
 
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4 STUDY OUTCOMES  
4.1 Primary Outcome 
Outcome 1: Immediate effect (Same day) of photodynamic treatment in combination with surgical 
antisepsis on bacterial skin colonization 
 
- 
Skin swabs:  
o Bacterial growth, density, and species before and immediately after PTD with 
standard 
bacterial 
cultures, 
MALDI-TOF 
for 
bacterial 
identification, 
semiquantitative amount of bacteria with dilution bacterial plates, molecular 
analysis using e.g RNA seq, whole genome sequencing 
- 
Skin biopsies 
o Changes of sebaceous and sweat glands after PDT (Histopathology with 
immunostaining) 
 
Outcome 2. Long-term effect (1 and 3 weeks after PDT treatment) on bacterial skin colonization 
in the groin after photodynamic treatment  
- 
Skin swabs:  
o Bacterial growth, density, and species before and immediately after PTD with 
standard 
bacterial 
cultures, 
MALDI-TOF 
for 
bacterial 
identification, 
semiquantitative amount of bacteria with dilution bacterial plates, molecular 
analysis using e.g RNA seq, whole genome sequencing 
- 
Skin biopsies 
o Changes of sebaceous and sweat glands after PDT (Histopathology with 
immunostaining) 
4.2 Secondary Outcomes 
Outcome 3: To evaluate phylogenetic similarity of same bacterial species before and after PTD 
based on the core genome analysis using whole genome sequencing 
- 
Phylogenetic analysis using whole genome sequencing of bacterial species 
4.3 Safety Outcomes 
Every PDT is documented as in routine clinics on a standardized protocol (see appendix 1).  
 
Clinical signs and symptoms after PDT as adverse events. We will distinguish between: 
- 
Mild redness and pain as to be expected (yes/no) 
- 
Advanced redness and pain more than expected (yes/no): adverse event.  
o “More than expected” is defined, if patients needs to take more than 1 
painkiller/day 
- 
Other signs and symptoms not expected (yes/no) 

 
 
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5 STUDY DESIGN AND COURSE OF STUDY 
5.1 General Study Design and Justification of the Design 
This is a pilotstudy of healthy volunteers, open label, and single center. If we see promising results 
in this pilotstudy, we will plan a prospective clinical trial in patients undergoing hip arthroplasty 
surgery. 
The intended procedures are photodynamic treatment (PDT) on the first day followed by skin 
swabbing and biopsies for control of skin microbiome of treated area immediately after the PDT 
(outcome 1) and by controlling 3 weeks after PDT (outcome 2).  
We think that this study design with healthy volunteers is adequate before starting a clinical trial.  
 
5.2 Study Duration and Study Schedule 
The expected duration of participant’s participation is 35 days from first study visit to the last 
follow-up time to report side effects of photodynamic treatment. The screening visit can be any 
time before but at least 1 week before the first study visit. The study schedule is indicated 
below.  
 
 

 
 
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Figure 1. Flow chart 
 
 
 
 
At the day of inclusion, the voluntary participant will be informed and asked for signing the 
informed consent by Dr. Yvonne Achermann when fulfilling in- and exclusion criteria. This visit 
and the last visit (day 35 of the study) will be at the outpatient clinic for Infectious Diseases at the 
University Hospital Zurich. Demographic data (age, sex, current medications, and underlying 
diseases) will be noted.  
Appointments for the photodynamic treatment (day 0) and the control visits (day  7 and 21) at the 
Department of Dermatology with Dr. L. Imhof or at the Infectious Diseases department will be 
made  
Study schedule:  
On day 0 with Dr. Imhof and Dr. Achermann, a skin scraping of the groin will be performed and 
sent for microbiological culture. Then, 5% topical methyl aminolevulinate (MAL) as the 
photosensitizer will be applied for 3 hours under occlusion in the right groin of the patient. After 
the incubation, the photodynamic process will be started by irradiation of the area with 40J/cm2 
red light from a 633nm emitting LED during 13 minutes.  
Immediately after the MAL-PDT, skin antisepsis will be performed. Antisepsis of the skin is 
performed with a povidone-iodine/alcohol solution (Betaseptic®, Mundipharma, Limburg, 
Germany) and repeated three times for a total duration of 3 minutes to imitate standard surgical 
antisepsis before a hip arthroplasty surgery. Skin scraping will be repeated after the 3rd antisepsis 
and 7 and 21 days later (study visit day 7 and 21) for bacterial cultures. 
As a control group, we will take skin swabs before and after skin antisepsis without PDT in 10 
participants. 
 

 
 
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On day 35 (±7 days) of the study, volunteers will be seen for the last study visit to document any 
adverse effects and to inform about the individual study result.  
 
Substudy in 5 volunteers: 
In the course of the study a total of three small skin biopsies are taken (3mm diameter each) from 
5 volunteers. The time and locations of the performed biopsies will be 
1. from the right groin immediately after the MAL-PDT or at day 7 
2. from untreated control area in the left groin after the MAL-PDT (day 0 or 7) 
3. from the MAL-PDT area on day 21 as the control after treatment.  
 
5.3 Methods of Minimizing Bias  
Excluded bias in our collective 
- 
No selected participants 
- 
Both sex can be included 
- 
Any age 
Potential bias in our collective: 
- 
Since we will search for healthy volunteers, the microbiome analysis might be slightly 
different to the population undergoing a hip arthroplasty surgery in an orthopedic hospital.  
6 STUDY POPULATION 
Twenty healthy male and female volunteers’ ≥ 18 years will be recruited for this clinical study. 
With the results of an ongoing trial investigating the effect of skin antisepsis before hip 
arthroplasty, we have a perfect comparator intervention group without the PDT intervention.  
An expected enrolment goal is 2-4 participants per month.  
6.1 Eligibility Criteria 
6.1.1 Inclusion Criteria 
Patients fulfilling all of the following inclusion criteria may be enrolled in the study 
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). 
6.1.2 Exclusion Criteria 
The presence of any one of the following exclusion criteria will lead to exclusion of the participant: 
 
Exclusion criteria: 
 
Pregnant and lacting women 

 
 
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 
Participants 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 14 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 
6.2 Recruitment and Screening 
Volunteers for this pilot study will be recruited by the Division of Infectious Diseases of the 
University Hospital Zurich with a flyer (appendix 2) as a recruitment tool (on pinboard at the 
University Hospital Zurich and the University Hospital Balgrist). Written informed consent will be 
taken under supervision of PD Dr. Y. Achermann.  
The participants will be informed in writing and verbal on: 
 
The nature, purpose and duration of, and procedure for the research project; 
 
Their right to withhold or to revoke their consent at any time without giving reasons; 
 
Their right to receive information at any time in response to further questions relating to the 
research project; 
 
Their right to be informed of results concerning their health, and their right for such 
information or to designate a person who is to take this decision for them; 
 
Measures to protect the biological material and the personal data 
 
All participants will have enough time to decide whether to participate or not (at least 1 week).  
The formal consent of a participant will be obtained before the participant is submitted to any 
study procedure. The consent form will be signed and dated by the investigator or his designee 
at the same time as the participant sign. A copy of the signed informed consent will be given to 
the study participant. The form will be retained as part of the study records in the patient file.  
 
There will be a financial compensation (value CHF 50.00) to the participants.  
6.3 Criteria for Withdrawal/ Discontinuation of Participants 
A participant must be withdrawn from the study if 
- 
safety reasons of PDT (other side effects than expected, or more intense known side 
effects).  
- 
participant consent withdrawal 
We need a minimal 10 to 15 participants to show the proof of principle of our study. Since we ask 
for 20 participant we can ask for 5 other participants if we had to exclude them.  
A participants who discontinued the study will be follow-up at least once after PDT treatment (3 
weeks) to ask for side effects. If no intervention was done, no follow-up is needed. 

 
 
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7 STUDY INTERVENTION 
7.1 General Information 
The following flowchart shows all steps described in the study plan:  
 
7.1.1 Study Intervention 
Study Intervention(s) A) 
 
Who 
List of interventions 
PD Dr. med. Yvonne Achermann 
Skin 
antisepsis, 
taking 
swabs 
in 
20 
participants 
Dr. med. Laurence Imhof 
Photodynamic treatment (see details below) in 
20 participants 
Skin biopsies (substudy) in 5 participants 
 
7.1.2 Control Intervention 
No control intervention in this study 
7.2 Administration of Study Intervention 
7.2.1 Study Intervention  
Details of study Intervention 
Justification 
1. Inguinal skin scraping before photodynamic treatment 
Baseline microbiome data 
2. Natural bacterial porphyrin fluorescence photography 
Baseline fluorescence photography 
3. Photosensitizer application, followed by fluorescence 
photography Photodynamic therapy (PHT) (1x) over 15 
minutes at the dermatology ward  
Treatment to kill bacteria and to 
reduce glands in order to reduce 
colonization bacteria 
4. Skin antisepsis in the groin, skin scraping after 
antisepsis 
To measure bacterial colonization to 
know the immediate effect of PDT 
5. Punch biopsy1 specimen of the MAL-PDT area 
(immediately after PDT) and of an untreated area as a 
control  
To analyze size and structure of 
glands in the skin 
6. Inguinal skin scraping and punch biopsy of the MAL-
PDT area after 7 and 21 days 
To measure bacterial colonization to 
know the long-term effect of PDT 
1 only in 5 participants 
 
7.2.2 Modification of Interventions 
Trial is not modifiable 

 
 
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7.3 Compliance with Intervention 
There will be no compliance problem of the study participant since the intervention takes place at 
visits 2 and 3. No intervention by the participant is needed except reporting of adverse effects. 
7.4 Data Collection and Follow-up for Withdrawn Participants  
Not applicable 
7.5 Concomitant Intervention(s) 
Since we only include participants for our analysis who do not take antibiotics or NSAR in the 14 
days prior to the photodynamic treatment or until follow-up at 14 days, we will inform on that issue 
at the screening and at each study visit. We will record it in our eCRF.  
The reason for this exclusion criteria is the impact on the bacterial skin flora and on inflammation 
in skin histopathology.  
8 STUDY PROCEDURES 
8.1 Study Flow Chart/Table of Study Procedures and Assessments 
Flow-chart see chapter 5.2.  
 

e 
Study plan: Effects of photodynamic therapy on the human inguinal skin microbiome to improve antiseptic effect 
 
Study tasks 
Screening 
Intervention Period 
Follow-up 
Visits 
1 
2 
3 
4 
5 
 
at least -7 
0 
7±3 
21±7 
35±7 
7. Participant information and informed consent 
 
 
 
 
 
8. Inclusion- and exclusion criteria 
 
 
 
 
 
9. Demographic data 
 
 
 
 
 
10. Inguinal skin scraping before photodynamic treatment 
 
 
 
 
 
11. Natural bacterial porphyrin fluorescence photography 
 
 
 
 
 
12. Study intervention: Photosensititer application, followed by 
fluorescence photography Photodynamic therapy (PHT) (1x) 
over 15 minutes at the dermatology ward  
 
 
 
 
 
13. Primary outcome measure: Skin antisepsis in the groin, 
skin scraping after antisepsis 
 
 
 
 
 
14. Secondary outcome measure: Punch biopsy1 specimen of 
the MAL-PDT area (immediately after PDT) and of an 
untreated area as a control  
 
 
 
 
 
15. Primary and secondary outcome measure: Inguinal skin 
scraping and punch biopsy1 of the MAL-PDT area  
 
 
 
 
 
16. (serious) adverse events 
 
 
 
 
 
17. End of study information of study results 
 
 
 
 
 
 1 optional, only in 5 volunteers 

Skin scrapping 
For all skin swabs, we will apply the scratching method using a scalpel as described previously 
(17) and illustrated below in Figure 2. The swabs and the biopsies will be analyzed for bacterial 
growth. The remaining sample will be immediately frozen at -80C° for later molecular analysis 
such as metagenomics. 
  
Figure 2. Specimen collection in the groin of the hip before disinfection. 
Skin scrapings will be removed with sterile blades and transferred to 
ESwab culture swabs (Copan).  
T, musculus tensor fascia latae; Tr, trochanter  
 
 
Photodynamic treatment 
This will be done by the dermatologist Dr. med. L. Imhof. She will apply 
5% topical methyl aminolevulinate (MAL) as the photosensitizer for 3 
hours under occlusion in the right groin of the participant. She will then start the photodynamic 
process by irradiation of the area with 40J/cm2 red light from a 633 nm emitting LED during 13 
minutes.  
Skin antisepsis 
After the MAL- photodynamic treatment, we will perform skin antisepsis as routinely done in clinics 
three times with a povidone-iodine/alcohol solution (Betaseptic®, Mundipharma, Limburg, 
Germany) for a total duration of 3 minutes to imitate standard surgical antisepsis before a hip 
arthroplasty surgery. We will perform skin scraping (see above) before and after the 3rd antisepsis 
and 21 days later for bacterial cultures.  
Skin Biopsies 
This will be done by the dermatologist Dr. med. L. Imhof in 5 volunteers. A small piece of skin (3 
mm) will be taken and transferred to a sterile tube for microbiological culture and 
histopathology. The skin biopsies will be taken after a local anesthesia. The wound will be 
closed with one stitch.  
8.2 Assessments of Outcomes  
8.2.1 Assessment of Primary Outcome  
What  
When 
How 
Bacterial density and species 
of skin swabs and biopsies 
Visit 2: immediate after 
intervention 
And Visit 3 
Microbiological diagnostic 
methods (see below) 
Histopathology 
Visit 2 (day 0) and Visit 3 
(after 21 days) 
Routine dermato-
histopathology 
 
Microbiology 
In short, the patient’s sample swabs will be streaked out onto Columbia sheep blood agar plate 
without antibiotics (bioMérieux, Mary-l’Etoile, France), colistin-nalidixic acid (CNA) blood agar 
(bioMérieux) plate for aerobic cultivation and a Brucella plate (in-house sheep blood agar plates 
with hemin and vitamin K1) for anaerobic cultivation using GENbag (bioMérieux). Final 
identification will be done by matrix-assisted laser desorption ionization-time of flight mass 
spectrometry spectrometry (MALDI-TOF MS) using a Bruker MALDI Biotyper. The amount of 
bacteria will be semiquantitiative described as +, ++, +++ based on growth on agar plates. All 
cultured microorganisms will be stored in skim milk at -80C° for potential subsequent analysis 
by whole genome sequencing for analyzing the secondary outcome.  

 
 
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Histopathology 
This part is to determine changes of eccrine gland lobules as a reduction in size, destruction or 
marked atrophy with molecular and immunofluorescence methods. In addition we will 
investigate the skin inflammation (type of immune cells, fibrosis).  
The participants of this substudy have to sign a separate informed consent document for taking 
the skin biopsies. 
8.2.2 Assessment of Secondary Outcomes 
For all persistent isolated microorganisms after PTD and antisepsis preparation of the skin will be 
subjected to whole genome sequencing for phylogenetic analysis based on core genome single 
nucleotide polymorphisms. To do so, chromosomal DNA of isolated bacteria will be extracted 
using the DNeasy UltraClean Microbial Kit (QIAGEN, Hilden, Germany) according to the 
manufacturer’s instructions. DNA library preparation is performed using the QIASeq FX Kit 
(QIAGEN). Pooled libraries will be sequenced on an Illumina MiSeq (paired-end sequencing, 2 x 
150 bp reads, 50-fold coverage). Raw sequencing data (FASTQ) will be processed using 
trimmomatic (41). Trimmed sequencing reads are assembled to CONTIGS using SPAdes (42). 
Core genome single nucleotid polymorphisms (SNPs) are determined by analyzing CONTIGS 
with parSNP (43). Concatenated SNPs are transformed into a multi-alignment file which 
eventually serves for the calculation of a phylogenetic tree by maximum likelihood (44). Whole 
genome sequencing, assembly and phylogenetic comparisons will be done at the Institute of 
Medical Microbiology (IMM) at the University of Zurich. 
 
What  
When 
How 
 
 
 
Whole Genome 
Sequencing/Phylogeny 
After termination of all study 
participants 
In collaboration with the 
Institute for Clinical 
Microbiology with a lot of 
experience in this field 
8.2.3 Assessment of Safety Outcomes 
8.2.3.1 
Serious Adverse Events  
Recording of serious adverse event (SAE) information time of onset, duration, resolution, action 
to be taken, assessment of intensity, and relationship with study intervention.  
8.2.4 Assessments in Participants who prematurely Stop the Study 
Participants who are withdrawn from the study prematurely due to adverse event, will be followed-
up until adverse-effects disappeared. Follow up may include but is not limited to physical 
examination, laboratory tests, vital signs, telephone calls. Outcomes and resolution of events will 
be recorded in the Case Report Forms. In case of lost to follow up, efforts will be made to contact 
the patient or to ascertain the vital status of the participant. 
8.3 Procedures at Each Visit 
8.3.1 Screening Visit = Visit 1 
Screening visit, Day – at least -7 days before the study start  
- 
Information of the study and all necessary study visits 
- 
Check for In- and Exclusion criteria 

 
 
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- 
Enrollment if agree to participate in study 
- 
Enter basic demographic parameters in electronic CRF (age, sex, current medications, and 
underlying diseases) 
- 
Scheduling of all study visits 
Duration: ca. 30 minutes 
Location: Division of Infectious Diseases, University Hospital Zurich 
 
Study schedule:  
 
Substudy in 5 volunteers: 
In the course of the study a total of three small skin biopsies are taken (3mm diameter each) from 
5 volunteers. The time and locations of the performed biopsies will be 
1. from the right groin immediately after the MAL-PDT or at day 7 
2. from untreated control area in the left groin after the MAL-PDT(day 0 or 7) 
3. from the MAL-PDT area on day 21 as the control after treatment.  
8.3.2 Visit 2 = Day 1 of the study 
On day 1 with Dr. Imhof and Dr. Achermann, a skin scraping of the groin will be performed and 
sent for microbiological culture. Then, 5% topical methyl aminolevulinate (MAL) as the 
photosensitizer will be applied for 3 hours under occlusion in the right groin of the patient. After 
the incubation, the photodynamic process will be started by irradiation of the area with 40J/cm2 
red light from a 633nm emitting LED during 13 minutes.  
Immediately after the MAL-PDT, skin antisepsis will be performed. Antisepsis of the skin is 
performed with a povidone-iodine/alcohol solution (Betaseptic®, Mundipharma, Limburg, 
Germany) and repeated three times for a total duration of 3 minutes to imitate standard surgical 
antisepsis before a hip arthroplasty surgery.  
For all inguinal swabs, we will use the scratching method using a scalpel as already applied in a 
previous study (ethical approval BASEC-Nr 2016-01017). The swabs will be sent to the 
microbiology laboratory of the University of Zurich for bacterial analysis (analysis under 
supervision of Prof. R. Zbinden).  
 
Skin biopsies will be done as a routine procedure at the Department of dermatology. 
In short: 
 
- 
Inguinal skin scraping before PDT 
- 
Natural bacterial porphyrin fluorescence photography 
- 
Study intervention: Photosensitizer application for 3 hours 
- 
PDT for 15 minutes 
- 
Inguinal skin scraping 
- 
Skin antisepsis with povidone/iodine (3xtimes for 1 minute) 
- 
Inguinal skin scraping 
- 
Punch biopsies in 5 participants 
- 
Documentation of adverse effects 
Duration: 4 hours 
Location: Department of dermatology, University Hospital Zurich 
 
8.3.3 Visit 3 (day 7±3) 
Skin scraping after skin antisepsis will be repeated 7 days later and analyzed for bacterial 
cultures.  
In short: 
- 
Inguinal skin scraping 

 
 
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- 
Skin antisepsis 
- 
Inguinal skin scraping  
- 
Punch biopsies in 5 participants 
- 
Documentation of adverse effects 
Duration: 30 - 60 minutes 
Location: Department of dermatology or Infectious Diseases, University Hospital Zurich 
 
8.3.4 Visit 4 (day 21±7) 
Skin scraping after skin antisepsis will be repeated 21 days later (study visit day 21) and analyzed 
for bacterial cultures.  
In short: 
- 
Inguinal skin scraping 
- 
Skin antisepsis 
- 
Inguinal skin scraping  
- 
Punch biopsies in 5 participants 
- 
Documentation of adverse effects 
Duration: 30 -60 minutes 
Location: Department of dermatology or Infectious Diseases, University Hospital Zurich 
8.3.5 Visit 5 = End of Study Visit (day 35±7) 
On day 35 (±7 days) of the study, volunteers will be seen for the last study visit to ask for side 
effects and to inform about the individual study result.  
In short: 
- 
End of study 
- 
Documentation of adverse effects 
- 
Information of the individual study results 
Duration: 30 minutes 
Location: Division of Infectious Diseases, University Hospital Zurich 
9 SAFETY 
During the entire duration of the study, all serious adverse events (SAEs) that may be causally 
related to the study intervention are collected and documented in source documents. Reportable 
events are recorded in the case report form (CRF). Study duration encompassed the time from 
when the participant signs the informed consent until the last protocol-specific procedure has 
been completed, including a safety follow-up period.  
In order to guarantee participants’ safety and health, further adverse events which must be 
documented or reported are to be designated in the protocol or at the request of the responsible 
CEC. 
9.1 Definitions 
Adverse events 
Adverse events (AEs) are defined as any untoward medical occurrence in a patient or clinical 
investigation participant after the intervention and which does not necessarily have a causal 
relationship with this treatment. An AE can therefore be any favorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease temporally associated with the 
intervention, whether or not related to the intervention. An AE may also consist of a new disease, 

 
 
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an exacerbation of a pre-existing illness or condition, a recurrence of an intermittent illness or 
condition, a set of related signs or symptoms, or a single sign or symptom. 
 
Serious Adverse Event 
A serious adverse event is defined as any event which: 
 
requires inpatient treatment not envisaged in the protocol or extends a current 
 
hospital stay; 
 
results in permanent or significant incapacity or disability; 
 
is life-threatening or results in death; or 
 
causes a congenital anomaly or birth defect. 
9.2 Recording and Assessment of Serious Adverse Events 
The investigator has the responsibility for SAE identification, documentation, and assessing the 
causal relationship study intervention. 
All SAEs will be fully documented in the appropriate eCRF. For each SAE, the investigator will 
provide the onset, duration, treatment required, outcome and action taken with regard to the study 
intervention.  
The assessment by the investigator with regard to the study intervention relation is done 
according to the following definitions: 
Unrelated 
 
The event started in no temporal relationship to the medical 
intervention applied and  
 
The event can be definitely explained by underlying diseases or other 
situations. 
Related 
 
 
The event started in a plausible temporal relationship to the medical 
intervention applied and  
 
The event cannot be definitely explained by underlying diseases or 
other situations. 
9.3 Reporting of Serious Adverse Events 
If, in the course of a clinical trial, serious adverse events occur in participants in Switzerland, and 
it cannot be excluded that the events are attributable to the intervention under investigation, the 
investigator must report these events: 
 
to the CEC within 15 days. 
 
Safety and protective measures 
If immediate safety and protective measures have to be taken during the conduct of this clinical 
trial, the investigator must notify the CEC of these measures, and of the circumstances 
necessitating them, within 7 days. 
 
Annual Safety Report  
All SAEs will be summed up in the annual safety report (ASR) and submitted to the CEC. ASR 
shall contain:  
- 
A summary of events including severity and causal relationship to the intervention and on 
the safety of participants. 

 
 
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- 
The accompanying letter provided with the Annual Safety Report should contain a short 
summary of the status of the clinical trial in Switzerland (number of centers open/closed, 
number of patients recruited/recruitment closed, and number of SAEs). 
9.4 Follow up of (Serious) Adverse Events 
Participants terminating the study (either regularly or prematurely) with 
 
reported ongoing SAE, or 
 
any ongoing AEs of laboratory values or of vital signs being beyond the alert limit 
will return for a follow-up investigation. This visit will take place up to 30 days after terminating the 
treatment period. Follow-up information on the outcome will be recorded on the respective SAE 
page in the eCRF.  
10 STATISTICAL METHODS  
Categorical data will be tested for differences using Fisher’s exact or chi-squared tests, as 
appropriate, whereas continuous variables will be tested using Wilcoxon rank sum tests. 
10.1 Hypothesis 
We hypothesize that photodynamic treatment improves skin antisepsis by reduction of 
persistent skin colonizing bacteria through the destruction of the sebaceous and sweat glands 
and by its bactericidal effects. 
10.2 Determination of Sample Size  
Aim: 20 volunteers to show the effect of PDT in healthy volunteers.  
10.3 Planned Analyses  
 
As a pilot study, we plan to do descriptive statistics only.  
 
Categorical date will be tested for differences using Fisher’s exact or chi-squared tests. 
 
Continuous variables will be tested using Wilcoxon rank sum tests.  
 
Data will be analyzed using Stata® version 14.2 (Stata Corporation, College Station, TX). 
Two-tailed P-values <0.05 are considered statistically significant. 
10.3.1 Datasets to be Analyzed, Analysis Populations 
All Study participants that terminated the study (n = max 20 volunteers) 
10.3.2 Primary Analysis 
Descriptive comparisons of microbiological data before and after PDT by Dr. Achermann, Dr. 
Kuster, and Dr. Zbinden.  
 

 
 
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10.3.3 Secondary Analyses 
Statistical analysis of microbiological data using whole-genome analysis: will be done by Dr. 
Achermann in collaboration with the Institute of Medical Microbiology.  
These analysis will be done after termination of all study participants 
10.3.4 Interim Analyses 
No interim analyses is needed for this small study design. 
 
10.3.5 Safety Analysis 
Analysis of SAE as standard (number of adverse and serious adverse events) 
 
10.3.6 Deviation(s) from the Original Statistical Plan  
Not applicable. 
10.4 Handling of Missing Data and Drop-Outs  
Missing outcome data will be handled as missing. No imputation methods will be used. 
11 ELIGIBILITY OF THE PROJECT SITE(S) 
PD Dr. med. Yvonne Achermann as the project leader is an Infectious Disease attending 
physician with a lot of experience in the field of orthopedic infections working at the University 
Hospital of Zurich and the Orthopedic University Hospital of Balgrist in Zurich. She will be 
responsible for the study design/protocol, perform skin swabs and and analyze microbiological 
cultures in collaboration with the institute for microbiology (IMM, with Prof. R. Zbinden). 
Dr. med. Laurence Imhof is the main investigator at the Department of Dermatology of the 
University Hospital Zurich. There she is the head of Laser Medicine, Photodermatology and 
Radiation Therapy. She has a lot of experience in photodynamic treatment and will therefore 
peform photodynamic treatment as indicated in the study plan. 
PD Dr. med. Stefan Kuster is a specialist in Infection Prevention and Control and Hospital 
Epidemiology (master of science in Clinical Epidemiology and Healthcare Research) and 
supervises the Swissnoso Surgical Site Infection Surveillance program at the University Hospital 
Zurich. He will be involved in the study design.  
PD Dr. med. Yvonne Achermann, Dr. med. Laurence Imhof, and PD Dr. med. Stefan Kuster are 
trained in Good Clinical Practice. 
Prof. Dr. med. Reinhard Zbinden provides the infrastructure for examining the skin swabs.  
12 DATA QUALITY ASSURANCE AND CONTROL 
The Sponsor-Investigator is implementing and maintaining quality assurance and quality control 
systems with written SOPs and Working Instructions to ensure that trials are conducted and data 
are generated, documented (record), and reported in compliance with the protocol, GCP, and 
applicable regulatory requirement(s).  

 
 
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12.1 DATA HANDLING AND RECORD KEEPING 
The study will strictly follow the protocol. If any changes become necessary, they must be laid 
down in an amendment to the protocol. All amendments of the protocol must be signed by the 
Sponsor-Investigator and if essential submitted to CEC.  
12.1.1 Case Report Forms  
The investigators will use electronic case report forms eCRF, one for each enrolled study 
participant, to be filled in with all relevant data pertaining to the participant during the study. All 
participants who either entered the study or were considered not-eligible or were eligible but not 
enrolled into the study additionally have to be documented on a screening log. The investigator 
will document the participation of each study participant on the Enrolment Log.  
For studies with electronic CRF: 
For data and query management, monitoring, reporting and coding an internet-based secure data 
base Redcap® developed in agreement to the Good Clinical Practice (GCP) guidelines will be 
used for this study. It is the responsibility of the investigator to assure that all data in the course 
of the study will be entered completely and correctly in the respective data base. Corrections in 
the eCRF may only be done by the investigator or by other authorized persons. In case of 
corrections the original data entries will be archived in the system and can be made visible. For 
all data entries and corrections date, time of day and person who is performing the entries will be 
generated automatically. 
CRFs/eCRFs will be kept current to reflect participant status at each phase during the course of 
study. Participants must not to be identified in the eCRF by name. Appropriate coded identification 
(e.g. Participant Number) will be used.  
We assure that any authorized person, who may perform data entries and changes in the eCRF, 
can be identified. A list with signatures and initials of all authorized persons will be filed in the 
study site file and the trial master file, respectively. 
The investigators assure to perform a complete and accurate documentation of the participant 
data in the eCRF. All data entered into the eCRF must also be available in the individual 
participant file either as print-outs or as notes taken by either the investigator or another 
responsible person assigned by the investigator.  
Essential documents must be retained for at least 10 years after the regular end or a premature 
termination of the respective study (KlinV Art. 45).  
Any patient files and source data will be archived for the longest possible period of time according 
to the feasibility of the investigational site, e.g. hospital, institution or private practice. 
12.1.2 Specification of Source Documents 
The following documents are considered source data, including but not limited to: 
 
SAE worksheets 
 
Nurse records, records of clinical coordinators, and  
Source data must be available at the site to document the existence of the study participants and 
substantiate the integrity of study data collected. Source data must include the original documents 
relating to the study, as well as the medical treatment and medical history of the participant. 
The following information (at least but not limited to) should be included in the source documents: 

 
 
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 
Demographic data (age, sex) 
 
Inclusion and Exclusion Criteria details  
 
Participation in study and signed and dated Informed Consent Forms  
 
Visit dates  
 
Microbiological data (identification of bacteria) 
 
SAEs (related) and concomitant medication  
 
Reason for premature discontinuation  
12.1.3 Record Keeping / Archiving  
All study data will be archived for a minimum of 10 years after study termination or premature 
termination of the clinical trial (at the Division of Infectious Diseases, University Hospital Zurich). 
12.2 Data Management  
All basic demographic data, all microbiological and histopathological results will be manually 
entered in an automatically secured online processing system (REDCap® electronic data 
capture system). The PI will check and validate data on a regular basis for consistency. 
All study data are encrypted in REDCap®. The principal investigator is responsible for data 
collection and will keep the screening log, which guarantees the confidentiality of data by the 
use of participant ID numbers. The participant ID numbers are automatically assigned in 
consecutive ascending form by the REDCap® system. For the purpose of fulfilling their task, the 
principal investigator grants the necessary access authorization in the form of user log-in and 
password to the study staff. Thus, the data cannot be altered in any way by unauthorized 
persons. In the REDCap® system, all relevant processing operations are documented in a user-
specific manner in order to ensure traceability. This is done by means of registration software, 
which records who has edited which data at which time. 
 
Whole genome sequencing data will be generated at the Institute of Medical Microbiology, 
University of Zurich. Data will be organized as follows: i) sequencing runs: 
YYMMDD_M04885_Run#_000000000-FlowCellID ii) samples: 
Sample#_S#_L001_[R1/R2]_001.fastq.gz. Data will be stored and managed on the Server of 
the Institute of Medical Microbiology. For analyses data will be copied to a LINUX-based 
workstation.  
 
All patients have to give their written consent to the project. These informed consents 
documents (IC) will be stored according to ethical regulations. 
 
Health related personal data captured during this project from participants are strictly 
confidential and disclosure to third parties is prohibited; coding will safeguard participants' 
confidentiality. Confidentiality will be ensured by using coded data. The code will be protected 
against unauthorized access and will be stored appropriately. Data will be stored for up to 10 
years after publishing the study as requested by most journals.  
 
 
Patient’s and microbiological/histopathological data:  
 
o Yvonne Achermann will be responsible for basic characteristics of the volunteers 
of this pilot study. After the last study visit, data will be encoded by the PI and 
safely stored at the Investigator Site File.  
o Clinical and microbiological data will be saved in the electronical database 
Redcap (see above) 
o The collected project data may be subject to inspection by the CEC. 
 

 
 
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 
Handling of isolated bacteria of the scrapped skin samples:  
The sub-cultivated bacterial samples will be stored and labeled with an encoded name at 
-80°C at the bacteriology laboratory of the Division of Infectious Diseases and Hospital 
Epidemiology (responsible Yvonne Achermann). The code for the bacterial strains with 
correspondence to patient data will be stored at the Investigator Site File. 
 
 
Handling of the skin tissue samples: 
o If the study patients agree, the remaining material from their skin samples will be 
kept for further research purposes in the Dermatological Biobank. If a study 
patient opposes the storage of skin sampling, they will be destroyed after the 
analyses planned as part of the study 
o Study patients receive a separate information leaflet for this purpose with the 
corresponding declaration of consent .The collection and storage of samples in 
the Dermatologische Biobank as well as the quality and safety standards are laid 
down in the regulations Dermatological Biobank USZ from the 1st of October 
2017 (Dermatologische Biobank EK 647) and become in this research project 
accordingly implemented 
12.3 Routine Monitoring 
Since we only measure microbiological data from skin samples, we think, that an interne 
monitoring would be adequate. This would include:  
- 
Microbiological study part (cultivation procedures) under supervision of Prof. Zbinden. 
Regular control of study result by a microbiologist not involved in the study (to be 
determined) 
- 
Data entry will be done by the doctorand and by the study nurse by a 4-eyes control. 
Control of data entry, informed consents, and SAE will be done by the sponsor and by 
Stefan Kuster (biometrician) on a regular base (4-eyes principle).  
12.4 Audits and Inspections 
A quality assurance audit/inspection of this study may be conducted by the CEC. The quality 
assurance auditor/inspector will have access to all medical records, the investigator's study 
related files and correspondence, and the informed consent documentation that is relevant to this 
clinical study. 
The investigator will allow the persons being responsible for the audit or the inspection to have 
access to the source data/documents and to answer any questions arising. All involved parties 
will keep the patient data strictly confidential. 
12.5 Confidentiality, Data Protection  
Direct access to source documents will be permitted for purposes of monitoring, audits and 
inspections. 
12.6 Storage of Biological Material and Related Health Data  
Data will be stored for up to 10 years after publishing the study as requested by most journals.  
 

 
 
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If the study patients agree, the remaining material from their skin samples will be kept for further 
research purposes in the Dermatological Biobank. If a study patient opposes the storage of skin 
sampling, they will be destroyed after the analyses planned as part of the study. 
Study patients receive a separate information leaflet for this purpose with the corresponding 
declaration of consent. The collection and storage of samples in the Dermatologische Biobank 
as well as the quality and safety standards are laid down in the regulations Dermatological 
Biobank USZ from the 1st of October 2017 (Dermatologische Biobank EK 647) and become in 
this research project accordingly implemented 
13 PUBLICATION AND DISSEMINATION POLICY  
After the statistical analysis of this trial the sponsor will make every endeavor to publish the data 
in a medical journal.  
Data of this study can only be published if Stefan Kuster, Reinhard Zbinden, Laurence Imhof, and 
Yvonne Achermann agree on the data presentation, analysis, and authors list.  
 
 Commitment for study coordination, ethical protocol, generate microbiological data, 
data entry, study analysis: Division of Infectious Diseases and Hospital Epidemiology, USZ (Dr. 
Achermann, Dr. Kuster, Steven Maurer under supervision of YA and SM) 
 Commitment for performing photodynamic treatment: Department of Dermatology, 
University Hospital Zurich (Dr. med. Laurence Imhof) 
 Commitment for bacterial culture, bacterial identification, storage: Institut of Medical 
Microbiology, UZH (Prof. Zbinden) 
The Principal Investigator will perform the study in accordance with the current protocol version. 
The Principal Investigator will ensure that any investigators and any other staff comply with the 
terms of the Protocol and this agreement. 
14 FUNDING AND SUPPORT  
14.1 Funding  
This study will be financed by the sponsor.  
External funding is provided by the Vontobel foundation for salary (study nurse and PhD student 
(CHF 
76’034) 
and 
by 
the 
Galderma 
company 
for 
the 
PDT 
treatment 
and 
microbiological/histolological examinations (CHF 11’323).  
14.2 Other Support  
15 INSURANCE 
Insurance is covered by “Versicherung für klinische Versuche und nichtklinische Versuche“ by 
Zürich Versicherungs-Gesellschaft AG (Policy no.: 14.970.888). 
Any damage developed in relation to study participation is covered by this insurance. So as not 
to forfeit their insurance cover, the participants themselves must strictly follow the instructions of 

 
 
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the study personnel. Participants must not be involved in any other medical treatment without 
permission of the principal investigator (emergency excluded). Medical emergency treatment 
must be reported immediately to the investigator. The investigator must also be informed instantly, 
in the event of health problems or other damages during or after the course of study treatment. 
The investigator will allow delegates of the insurance company to have access to the source 
data/documents as necessary to clarify a case of damage related to study participation. All 
involved parties will keep the patient data strictly confidential. 
A copy of the insurance certificate will be placed in the Investigator’s Site File. 
 
 

 
 
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16 REFERENCES 
Awad, M. M., A. Tovmasyan, J. D. Craik, I. Batinic-Haberle and L. T. Benov (2016). "Important cellular 
targets for antimicrobial photodynamic therapy." Appl Microbiol Biotechnol 100(17): 7679-7688. 
Berrios-Torres, S. I., C. A. Umscheid, D. W. Bratzler, B. Leas, E. C. Stone, R. R. Kelz, C. E. Reinke, S. 
Morgan, J. S. Solomkin, J. E. Mazuski, E. P. Dellinger, K. M. F. Itani, E. F. Berbari, J. Segreti, J. Parvizi, J. 
Blanchard, G. Allen, J. Kluytmans, R. Donlan, W. P. Schecter and C. Healthcare Infection Control Practices 
Advisory (2017). "Centers for Disease Control and Prevention Guideline for the Prevention of Surgical Site 
Infection, 2017." JAMA Surg 152(8): 784-791. 
Borgia, F., R. Giuffrida, E. Caradonna, M. Vaccaro, F. Guarneri and S. P. Cannavo (2018). "Early and Late 
Onset Side Effects of Photodynamic Therapy." Biomedicines 6(1). 
Bratzler, D. W., E. P. Dellinger, K. M. Olsen, T. M. Perl, P. G. Auwaerter, M. K. Bolon, D. N. Fish, L. M. 
Napolitano, R. G. Sawyer, D. Slain, J. P. Steinberg, R. A. Weinstein, P. American Society of Health-System, 
A. Infectious Diseases Society of, S. Surgical Infection and A. Society for Healthcare Epidemiology of 
(2013). "Clinical practice guidelines for antimicrobial prophylaxis in surgery." Surg Infect (Larchmt) 14(1): 
73-156. 
Dumville, J. C., E. McFarlane, P. Edwards, A. Lipp and A. Holmes (2013). "Preoperative skin antiseptics 
for preventing surgical wound infections after clean surgery." Cochrane Database Syst Rev(3): CD003949. 
Dumville, J. C., E. McFarlane, P. Edwards, A. Lipp, A. Holmes and Z. Liu (2015). "Preoperative skin 
antiseptics for preventing surgical wound infections after clean surgery." Cochrane Database Syst Rev(4): 
CD003949. 
Lee, M. J., P. S. Pottinger, S. Butler-Wu, R. E. Bumgarner, S. M. Russ and F. A. Matsen, 3rd (2014). 
"Propionibacterium persists in the skin despite standard surgical preparation." J Bone Joint Surg Am 96(17): 
1447-1450. 
Matsen, F. A., 3rd, S. M. Russ, A. Bertelsen, S. Butler-Wu and P. S. Pottinger (2015). "Propionibacterium 
can be isolated from deep cultures obtained at primary arthroplasty despite intravenous antimicrobial 
prophylaxis." J Shoulder Elbow Surg 24(6): 844-847. 
Pulido, L., E. Ghanem, A. Joshi, J. J. Purtill and J. Parvizi (2008). "Periprosthetic joint infection: the 
incidence, timing, and predisposing factors." Clin Orthop Relat Res 466(7): 1710-1715. 
Sakamoto, F. H., J. D. Lopes and R. R. Anderson (2010). "Photodynamic therapy for acne vulgaris: a critical 
review from basics to clinical practice: part I. Acne vulgaris: when and why consider photodynamic 
therapy?" J Am Acad Dermatol 63(2): 183-193; quiz 193-184. 
Tande, A. J. and R. Patel (2014). "Prosthetic joint infection." Clin Microbiol Rev 27(2): 302-345. 
 
 

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17 APPENDICES 
 
Appendix 1: Documentation of PDT as in routine clinics at the clinic for dermatology 
 
 

 
 
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Appendix 2. Flyer 
Auswirkungen der Lichttherapie auf Hautbakterien 
 
 
Probandinnen und Probanden gesucht 
 
Für eine wissenschaftliche Studie suchen wir Frauen und Männer mit 
Mindestalter 18 Jahre für die Untersuchung der Hautbakterien vor und 
nach einer Lichttherapie. 
 
 
1) 
Ziel der Studie: Es ist bekannt und natürlich, dass Bakterien die ganze Haut – inklusive 
Schweiss- und Talgdrüsen - kolonisieren. Vor Operationen wird die Haut desinfiziert um diese 
Bakterien abzutöten. Leider ist diese Präventionsmassnahme nicht 100% effektiv. Die Gefahr 
besteht, dass noch vorhandene Bakterien mit dem chirurgischen Schnitt in die Tiefe vorschleppt 
werden und dort eine Infektion verursachen kann. Aus diesem Grund müssen die gegenwärtigen 
Desinfektionsprozesse hinterfragt und verbessert werden. Mit dieser Studie am Universitätsspital 
Zürich untersuchen wir, ob die Lichttherapie Hautbakterien abtöten und dieTalg- und 
Schweissdrüsen in der Haut verkleinern kann. Diese Therapie ist auf der Klinik für Dermatologie 
etabliert, wird gut vertragen und es entstehen keine Folgeschäden.  
 
Ablauf: Die Studienteilnahme beinhaltet 4 Termine innerhalb von 5 Wochen. Diese finden 
entweder in der Klinik für Infektionskrankheiten oder der Klinik für Dermatologie statt. Der erste 
Termin dauert ca. 20 Minuten und dient der Studienaufklärung und Abklärung zur Teilnahme. Der 
zweite Termin dauert 4 Stunden und beinhaltet die Lichttherapie mit Hautabstrichen vor und 
nachher. Die dritte und vierte Visite dauert zwischen 15 und 30 Minuten zur Kontrolle der 
Hautbakterien und zum Studienabschluss.  
 
 
Alle Daten werden vertraulich behandelt. Für die Versuchspersonen ergibt sich kein direkter 
medizinischer Nutzen. Es gibt eine Entschädigung von CHF 50.00 für die Teilnahme. Alle 
Untersuchungen sind kostenlos.  
 
Wir würden uns freuen, wenn Sie an einer Studienteilnahme interessiert sind. Sie können gerne 
per Email oder telefonisch mit PD Dr. Yvonne Achermann Kontakt aufnehmen: 
 
yvonne.achermann@usz.ch;  
Tel: +41 44 255 34 02 direkt oder übers Sekretariat (044 255 33 22) 
 
 
Bitte nehmen Sie zur Kenntnis, dass ihre Daten bei Zustandekommen eines Kontakts registriert 
werden. Sollten Sie später nicht einer Teilnahme interessiert sein, werden ihre Daten 
unverzüglich gelöscht.  
 
 
 
Dieses Projekt ist organisiert durch:  
PD Dr. med. Yvonne Achermann, Klinik für Infektionskrankheiten, Universitätsspital Zürich und 
Dr. med. Laurence Imhof, Klinik für Dermatologie, Universitätsspital Zürich