Dear Sir, Nadifloxacin** Registered in Germany as Nadixa, Ferrer International S.A., Gran Via Carlos III, 94, ES-08028 Barcelona, Distributor: Dr. Pfleger Arzneimittel GmbH. (OPC-7251) represents an established antimicrobial agent belonging to the quinolone group and was developed exclusively for topical administration4. Nadifloxacin is effective in treating a variety of bacterial skin infections and acne.2, 3, 5, 7-9 Here, the in vitro activity of nadifloxacin was assessed and compared with those of erythromycin, clindamycin and tetracycline against Cutibacterium (C.) acnes, formerly Propionibacterium acnes, to gain a picture of the resistance situation in Germany. The study was approved by the Ethics Committee of the Bayerische Landesärztekammer (Munich, Germany; EC-No.17088) and registered at Deutsches Register Klinische Studien (ID: DRKS00014231). Samples were collected between March and May 2018 at 45 sites. Each sample was obtained from a pustule of the facial area using a sterile sample collection swab and directly inserted in the transport tube medium (Amies medium, Sarstedt AG & Co. KG, Nümbrecht, Germany, order number 80.1361.500). Further information was acquired to characterize the patient population, acne score (Leeds revised Acne Grading System6) and prior antibiotic treatment of acne. The VITEK 2 ANC Card System for Identification of Clinical Isolates of Anaerobic Bacteria (bioMérieux sa, Marcy-l´Etoile, France, distributed by bioMérieux Deutschland GmbH, Nürtingen, Germany) was used. Reference standards of antimicrobial agents were purchased by Sigma-Aldrich Chemie GmbH (Taufkirchen, Germany): nadifloxacin (Order no. SMB00375-1G), clindamycin phosphate (Order no. PHR1021-1G), erythromycin (Order no. E5389-1G) and tetracycline hydrochloride (Order no. T7660-5G). Nadifloxacin was dissolved in 0.1 N NaOH, erythromycin in ethanol 96% (Dr. K. Hollborn & Söhne GmbH & Co. KG, Leipzig, Germany), clindamycin and tetracycline in sterile distilled water. Before susceptibility testing, the isolates were transferred on Columbia 5% SB (sheep blood) agar (BD, Heidelberg, Germany) to ensure purity and good growth. The antimicrobial susceptibility against the different drugs was determined by an agar dilution method using Gifu Anaerobic Medium agar modified ‘Nissui’ (Nissui Pharmaceutical Inc. Ltd., Tokyo, Japan; pH 7.3, distributed by HyServe GmbH & Co. KG, Uffing, Germany) and a bacterial cell inoculum of 106 cfu per ml as it was previously described5. The plates were incubated at 37°C in anaerobic atmosphere using the Anaerocult system (Merck, Darmstadt, Germany) and analysed after 48 h incubation for anaerobic C. acnes. Minimum inhibitory concentration for clindamycin was determined by E-test (Liofilchem, Roseto degli Abruzzi, Italy) on Mueller-Hinton agar plates (BD, Heidelberg, Germany), which covered a continuous concentration range from 0.016 to 256 µg/mL. Two control organisms (C. acnes DSM 1897 and 108415, Braunschweig, Germany) were tested simultaneously (MIC [µg/mL]: nadifloxacin: 0.195; erythromycin: 0.049; tetracycline: 0.78; clindamycin: 0.016; [n = 2]). A total of 73 strains of C. acnes from 115 samples were isolated. Of these 73 samples, 23 (31.5%) came from patients who had been pretreated with antibiotics. More than half of the patients (51.4%) were ≤21 years old (Table 1). Most of the patients suffered from mild to moderate acne, represented by a Leeds score of 6 for the 3rd quartile (75%) and 4 for the median (Table 1).6 None of the 73 strains revealed elevated minimum inhibitory concentration (MIC) levels against nadifloxacin or tetracycline. Table 2 shows the number of samples in which resistance was detected according to the applied clinical breakpoints. The highest percentage (15.07%, 11 strains) was shown for erythromycin, followed by clindamycin (4.11%, 3 strains). MIC range (min to max) [µg/mL] MIC50 [µg/mL] MIC90 [µg/mL] Breakpoint resistance [µg/mL] % resistance (no. of strains) ≥2‡‡ Sardana et al. 8. ≥8†† Alba et al. 1. For both breakpoints: 15.07 (11) As for erythromycin a significant number of resistances was found (n = 11), an investigation into possible influencing factors on occurrence of resistant strains was carried out by means of contingency tables. There is no evidence of an influence of age, severity of acne or antibiotic pretreatment on the occurrence of resistant strains. In summary, nadifloxacin was found to be highly active against C. acnes isolated from patients with acne vulgaris. However, a considerable number of C. acnes strains showed in vitro resistance against erythromycin and clindamycin. We thank Dr. Anna Derr for proofreading the manuscript (Department Medical Science/Clinical Research, Dr. Pfleger Arzneimittel GmbH, Bamberg, Germany). C Neumeister, M R Götz and U Schwantes are employees of Dr. Pfleger Arzneimittel GmbH. P Nenoff, D Koch and C Krüger are employees of the laboratory for medical microbiology, which was commissioned by Dr. Pfleger Arzneimittel GmbH with the isolation of C. acnes and susceptibility testing. R-H Bödeker and C. Borelli have received honoraria for their advisory activities from Dr. Pfleger Arzneimittel GmbH. This study was funded by Dr. Pfleger Arzneimittel GmbH, Bamberg, Germany.

Background Considering the increasing number of chemical peeling applications, also the interest in the history of chemical peelings and agents, has grown in dermatology. Research ascribes the first use of phenol as a chemical peeling agent to William Tilbury Fox (1836-1879) in 1871. Furthermore, Ferdinand von Hebra (1847-1902) is said to describe the properties of various peeling agents in 1874, and Paul Gerson Unna (1850-1929) adds resorcinol and trichloroacetic acid in 1882. Objective To identify the first mentions of chemical peeling applications and agents in 19th-century dermatology. Methods Nineteenth-century dermatologists were identified by an examination of literature of the last 30 years on the history of chemical peeling. Systematic examination of the medical textbooks of Hebra, Fox and Unna was conducted. It was proved whether the mentioned agents were used for chemical peeling applications. Results The skin peeling property of phenol was already discovered by its first describer, the chemist Friedlieb Ferdinand Runge (1795-1867) in 1834. The Viennese dermatologist Hebra described phenol as a chemical peeling agent in 1860. Hebra and his associate Moriz Kaposi (1837-1902) stated that 'Lotio carbolica' was already used in London. Fox used phenol mostly as a disinfectant and not for chemical peelings since 1869. Unna described the chemical peeling property of salicylic acid in 1882 and gave the most comprehensive account of chemical peels of the 19th century in 1899. Unna also introduced the Gutta-percha plaster with salicylic acid and phenol. Around 1900, Unna was famous for his peeling paste with resorcinol in Germany. Conclusions A new chronology of the introduction of chemical peeling in dermatology can be drawn from the results. The German-speaking dermatology pioneered the treatment of skin diseases with chemical peelings as well as for aesthetical purposes 21 years earlier than hitherto known.

Background Recipes for peelings date back to medical texts of old Egypt. The oldest medical papyri contain recipes for improving beauty of the skin' and removing wrinkles' by use of agents such as salt and soda. The Egyptian Queen Cleopatra (69-30 BC) is said to have taken bathes in donkey's milk to improve the beauty of her skin. However, little is known about other agents and peeling applications in later Greek medical textbooks. ObjectiveMethodsWe will discover new agents and describe ancient peeling applications. First, we will have to identify ancient Greek medical terms for the modern terms peeling' and chemical peeling'. Second, on the basis of the identified terms, we will perform a systematic full-text search for agents in original sources. Third, we will categorize the results into three peeling applications: (i) cleansing, (ii) aesthetical improvement of the skin and (iii) therapy of dermatological diseases. We performed a full systematic keyword search with the identified Greek terms in databases of ancient Greek texts. Our keywords for peeling and chemical peeling are smexis' and trpsis'. Our keywords for agents of peeling and chemical peeling are smegmata', rhymmata', kathartika' and trimmata'. ResultsConclusionDiocles (4th century BC) was the first one who mentioned smexis' and trpsis' as parts of daily cleansing routine. Criton (2nd century AD) wrote about peeling applications, but any reference to the agents is lost. Antyllus (2nd century AD) composed three lists of peeling applications including their agents. Greek medical textbooks of Graeco-Roman antiquity report several peeling applications such as cleansing, brightening, darkening, softening and aesthetical improvement of the skin by use of peeling and chemical peeling, as well as therapy of dermatological diseases. There are 27 ancient agents for what is contemporarily called peeling and chemical peeling. We discovered more specific agents than hitherto known to research.

Background Recently, therapy of rosacea with inflammatory lesions (papulopustular) has improved substantially with the approval of topical ivermectin 1% cream. It is assumed to have a dual mode of action with anti-inflammatory capacities and anti-parasitic effects against Demodex, which however has not yet been demonstrated in vivo. Aim To find scientific rationale for the dual anti-inflammatory and anti-parasitic mode of action of topical ivermectin 1% cream in patients with rosacea. Methods A monocentric pilot study was performed including 20 caucasion patients with moderate to severe rosacea, as assessed by investigator global assessment (IGA score >= 3) and a Demodex density >= 15/cm(2). Patients were treated with topical ivermectin 1% cream once daily (Soolantra (R)) for >= 12 weeks. The density of Demodex mites was assessed with skin surface biopsies. Expression of inflammatory and immune markers was evaluated with RT-PCR and by immunofluorescence staining. Results The mean density of mites was significantly decreased at week 6 and week 12 (P < 0.001). The gene expression levels of IL-8, LL-37, HBD3, TLR4 and TNF-alpha were downregulated at both time points. Reductions in gene expression were significant for LL-37, HBD3 and TNF-alpha at both follow-up time points and at week 12 for TLR4 (all P < 0.05). Reduced LL-37 expression (P < 0.05) and IL-8 expression were confirmed on the protein level by immunofluorescence staining. All patients improved clinically, and 16 of 20 patients reached therapeutic success defined as IGA score <= 1. Conclusion Topical ivermectin 1% cream acts by a dual, anti-inflammatory and anti-parasitic mode of action against rosacea by killing Demodex spp. in vivo, in addition to significantly improving clinical signs and symptoms in the skin.

Topical monotherapy is a valid therapeutic approach in onychomycosis. Due to its lengthy course and its non-reimbursed product status, cost and compliance are important issues and non-pharmacological properties such as over-the-counter price and ease of use should be considered when deciding which product to recommend. We investigated surrogate parameters for patient-friendliness and treatment cost in Germany in a questionnaire-based prospective, comparative, intra-individual, open-label trial of the two common topical antifungal nail lacquers Loceryl(®) (amorolfine 5%) and Ciclopoli(®) (ciclopirox 8%) in eight patients with clinically diagnosed onychomycosis. The 2.5 ml bottle of Loceryl(®) covered a treatment period of 308 days, resulting in treatment costs of €0.10 per day in comparison to the 3.3 ml bottle of Ciclopoli(®), covering 127 days at €0.21 per day, given once-daily application for Ciclopoli(®) and once-weekly application for Loceryl(®) in accordance with regulatory approval. Six out of eight patients favoured the Loceryl(®) treatment regimen. Furthermore, four out of eight patients found Loceryl(®) easier to apply, whereas three preferred Ciclopoli(®). In total, seven out of eight stated a clear preference for Loceryl(®) over Ciclopoli(®). Loceryl(®) therapy is less expensive and less time-consuming. The therapeutic period that can be covered is longer and more patients stated a clear preference for Loceryl(®) in comparison to Ciclopoli(®). The differences are statistically significant, underlining probable clinical relevance.

Background The difficulty of antifungal substances to penetrate keratin and slow nail growth limit the efficacy of topical therapy in onychomycosis. One promising alternative is photodynamic antimicrobial chemotherapy, or PACT : an irradiated photosensitizer creates singlet oxygen molecules which destroy pathogens without damaging human cells. Objective As PACT has demonstrated strong antifungal capabilities, we wanted to investigate its efficacy in an in vitro model of onychomycosis. Methods PACT was tested in a microdilution assay, in an in vitro onychomycosis model as well as in a patient. Results PACT inhibited fungal growth in the microdilution assay with no colonies of T. rubrum detectable. Fungal growth was also inhibited in an onychomycosis model, after 30 min of LED irradiation. Subsequently, a patient with distolateral onychomycosis was treated on three consecutive days and showed significant and durable improvement of nail morphology 6 months after. Conclusion PACT appears to be an effective treatment of onychomycosis in vitro . The promising results need to be validated by clinical trials.

Rosacea is like no other disease a problem for patients regarding the use of skin care and cleaning products. The subjective assessment of the severity of the illness is an important factor regarding the development of depression in these patients. Inadequate skin care and cleaning products can lead to irritation and stinging of the skin. Dermatologists should address questions regarding skin care, cleaning and sun screens. Because of the higher irritability of the skin of rosacea patients, all possibly irritating cleaning products or procedures should be avoided. The water temperature is also important; it should be lukewarm to avoid the provocation of a vascular reaction. Soaps should be avoided, because they are alkaline and thus lead to a higher pH of the skin. A higher pH of the skin can lead to irritation. Appropriate make-up causes no aggravation of the skin and increases patient's satisfaction with their skin and thus leads to a higher compliance with pharmacological therapy. Laser or intense pulsed light treatment can improve telangiectasia or erythema. Operative treatment of rhinophyma is effective and well-established.

SynopsisThe aim of this study was to evaluate different urea‐containing cosmetic preparations designed for foot care regarding skin occlusion. The primary aim was therefore to screen the short‐term transepidermal water loss (TEWL) as a parameter for skin barrier function and skin occlusion and to characterize the relative role of the vehicle, i.e. cream or foam in the context of cosmetics containing urea in the 2–10% range addressing the cosmetic products urea 2% cream (GEHWOL FUSSKRAFT blau), petrolatum containing cream (GEHWOL med Schrundensalbe), urea 10% cream (GEHWOL med Lipidro‐Crème), urea 10% foam (Allpresan Fuss Schaum) and vaseline (positive control) compared with an untreated area on the volar forearms of volunteers. Moreover, the short time (24 h) kinetics regarding the moisturizing effect of cream and foam formulations in diabetic patients were compared. The efficacy of a cream on reduction of skin thickness of hyperkeratotic skin in the heel region before and after a period of product application was also evaluated. In some of the trials, healthy individuals and in others, diabetic patients (type I and II) were enrolled. TEWL was determined before product application, as well as at given points of time thereafter. In this study, no excessive occlusion effects comparable with a blockage of the skin’s natural water evaporation could be observed for any of the test products. To the extent to be expected, this was found neither for the cream products nor for the foam product. Slightly lowered TEWL values after application of the 10% urea cream can be interpreted as a beneficial effect in terms of an improved barrier function. Regarding skin moisture, the urea‐containing cream formulation appeared equal or slightly superior to the foam formulation. The thickness of the horny layer was found reduced after application of 10 % urea‐containing cream. At present it looks as if cream vehicles would still be vehicles of choice in general, when it comes to the formulation of skin care preparations for not only dry skin but also in the context of pedal skin care.

Die Rosazea stellt wie kaum eine andere Erkrankung ein Problem für die betroffenen Patienten bezüglich der Auswahl ihrer Hautreinigungs- und Hautpflegeprodukte dar. Außerdem ist die subjektive Einschätzung des Schweregrads ihrer Erkrankung entscheidend für die psychische Belastung durch die Rosazea. Ungeeignete Pflege und Hautreinigung kann zu Irritationen und Missempfindungen der Haut führen. Die betreuenden Dermatologen sind hier als Ansprechpartner bezüglich Beratung zu geeigneten Hautpflege-, Hautreinigungs- und UV-Schutzprodukten besonders gefragt. Aus der erhöhten Empfindlichkeit der Haut bei Rosazeapatienten ergibt sich, dass auf jegliche aggressive Substanzen oder Reinigungsprozeduren zu verzichten ist. Insofern ist auch schon die Wassertemperatur entscheidend, die lauwarm sein sollte, um eine Gefäßreaktion zu vermeiden. Auf Seifen ist zu verzichten, da diese alkalisch sind und den pH der Haut erhöhen. Eine pH-Anhebung kann zu Irritationen der Haut führen. Geeignete abdeckende Kosmetik führt zu keiner Verschlechterung des Hautbefundes und erhöht die Zufriedenheit der Patientinnen und Patienten mit ihrem Hautbild und erhält damit die Compliance der Patienten bei Durchführung der medikamentösen Therapie. Eine Besserung der Teleangiektasien und Rötung bei Rosazea lässt sich durch geeignete Laser- oder Blitzlampentherapie erreichen. Eine operative Sanierung von Phymen ist möglich und wird beim Rhinophym regelmäßig eingesetzt.