The effect of Staphefekt on the skin microbiome, including Staphylococcus aureus, in patients with atopic dermatitis.

Staphylococcus aureus (S. aureus) is both a commensal and a pathogenic
organism. Carriage of S. aureus is not harmfull per se, however there is a risk
of autoinfection. The bacteria is responsible for the vast majority of skin
infections, such as impetigo and infection of wounds. Also colonization with S.
aureus is related to atopic dermatitis. Increasing multidrug resistance of S.
aureus points out the need for development of alternative treatment options for
bacterial infections. Gladskin is a product for topical use. The proprietary
enzyme in the Gladskin products is called Staphefekt. Staphefect specifically
lyses the cell membrane of Staphylococcus aureus. In vitro results showed that
Staphefekt kills S. aureus, leaving the commensal flora intact. Staphefekt
might decrease S. aureus colonisation of the skin and consequently decrease
occurrence of and/or symptoms of S. aureus related disease.

To retrieve (in vivo) data about the effect of Staphefekt on the microbiome,
including Staphylococcus aureus, and on disease severity in patients with
atopic dermatitis.

A single centre intervention study with a placebo controlled, double blind and
randomized design.

30 patients are recruited and characterized. Characterization of patients
includes (1) determination of S. aureus colonization status by screening the
nares, the pharynx and the lesional skin (preferably left and right
anticubital folds) and (2) evaluation of patient characteristics using a
questionnaire addressing e.g. history of skin disease. Of the 30 patients, 16
colonized patients and 6 non-colonized patients will be included in the study.
The intervention includes application of Staphefekt or placebo in the nose and
on the skin lesions (anticubital folds), twice daily during 3 weeks. Microbiome
of the nose and skin and disease severity will be measured at baseline, right
after the first application and one and three weeks later. Isolation of S.
aureus and other skin bacteria is performed by culture, QPCR and 16S rRNA
sequencing. Disease severity will be assessed using the EASI and Self
Administrated-EASI. Seven days after application of Staphefekt side-effects are
evaluated through a questionnaire.

Risks: Based on current literature, internal assessments and evaluations by ETH
(Eidgenössische Technische Hochschule, Zurich, Switzerland) it can be
concluded that Staphefekt is safe for its targeted applications on the skin.
This is evaluated externally by TNO. TNO concludes that endolysins can be used
safe as medical device in the treatment of (MR)SA on the skin. In animal
testing no adverse side effects of lysins are seen. There is a possibility of a
contact allergic reaction to other basic components (cera cetomacrogol) of the
product or the swab solution (tween).
Benefit: Participation in this study might result in individual benefit for the
patient, as Staphefekt might reduce S. aureus load on the skin/mucosa. Flares
in patients with eczema are associated with higher loads of S. aureus.
Burdening: The study includes 5 visits within 5 weeks of time. During the first
visit (30 minutes) patients are screened on in- and exclusion criteria,
informed consent is obtained, patient characteristics are evaluated and skin
and nasal swabs are taken. The second visit (10 min) includes a skin and nasal
swab. During the third visit the researcher assesses the patients skin, the
patients fills in a questionnaire and swabs are taken from the skin (before
application of Gladskin, 1 hour after application and 6 hours after
application). The fourth and fifth visit (30 minutes) includes assessment of
disease severity and performing a skin- and nasal swab. Screening for S. aureus
is performed using swabs, a non-invasive method. Psychological discomfort is
kept to a minimum by letting subjects perform the perineum swab themselves
(after verbal instruction).