Bifonazol – In-vitro-Wirksamkeit gegenüber Corynebacterium minutissimum – ein Update zur Diagnostik und Therapie des Erythrasmas

Zusammenfassung

Corynebacterium minutissimum wird als bakteriologische Ursache des Erythrasmas angesehen. Die Behandlung erfolgt mit topischen, manchmal systemischen Antibiotika, häufiger jedoch mit topischen Antimykotika aus der Gruppe der Imidazole. Neben Clotrimazol ist das vor allem Bifonazol, welches für diese Indikation zugelassen und wirksam ist. Es wurden 24 Stämme unterschiedlicher Corynebacterium-Arten, darunter Corynebacterium (C.) minutissimum, sowie einzelne Stämme von weiteren grampositiven Bakterien-Spezies, hinsichtlich ihrer In-vitro-Empfindlichkeit gegenüber Bifonazol untersucht. Zur Anwendung kam ein Agardilutionstest, mit dessen Hilfe minimale Hemmkonzentrationen (MHK) für Bifonazol bestimmt werden können.

Bifonazol zeigte gegenüber allen getesteten Corynebacterium-Spezies und -Stämmen eine sehr gute In-vitro-Aktivität. Die MHK-Werte lagen bei 0,05 bis 1,56 µg/ml⁻¹ (10⁶ KbE/ml⁻¹). Bei einer Bakteriendichte von 10⁸ KbE/ml⁻¹ ergaben sich MHK-Werte von 0,1 bis 1,56 µg/ml⁻¹. Es hat sich gezeigt, dass Bifonazol in vitro eine sehr gute Wirksamkeit gegenüber Corynebacterium spp. hat. Das betrifft offensichtlich nicht nur C. minutissimum, sondern auch die anderen – hier getesteten – Corynebacterium-Arten. Das waren C. accolens, C. argentoratense, C. jeikeium, C. macginleyi, C. propinquum und C. pseudotuberculosis.

Abstract

The gram-positive bacteria Corynebacterium minutissimum are known as causative agent of the erythrasma. The treatment is based on the application of topical antibiotics, sometimes oral antibiotics have to be used. However, more frequently, topical antifungal agents of the imidazole group are used for erythrasma. This is, after clotrimazole, first of all bifonazole, which is approved for treatment of this superficial bacterial infection of the skin, and has been shown to be efficient in this dermatosis.

Altogether, 24 strains of different species of the genus Corynebacterium, among them Corynebacterium (C.) minutissimum, and single strains of further species of other gram-positive bacteria, were investigated for their in vitro susceptibility against bifonazole. An agar dilution test was used for determination of minimum inhibitory concentration (MIC) of bifonazole.

Bifonazole showed a very good in vitro activity against all tested species and strains of Corynebacterium. MIC values were in a range from 0.05 until 1.56 µg ml⁻¹ (10⁶ cfu [colony forming units] ml⁻¹). At a higher densitiy of bacteria (10⁸ cfu ml⁻¹) MIC values at a range from 0.1 until 1.56 µg ml⁻¹ were found. In conclusion, it could be demonstrated that bifonazole exhibits a very good in vitro activity against Corynebacterium spp.

Obviously, this concerns not only the species C. minutissimum, but also the other tested species of Corynebacterium, which were C. accolens, C. argentoratense, C. jeikeium, C. macginleyi, C. propinquum, and C. pseudotuberculosis.

• Literatur

• 1 Earl D, Allenby L, Richards H et al. Bifonazole 1% gel in the treatment of superficial dermatophytoses and erythrasma of the feet and groin. Pharmatherapeutica 1986; 4: 532-535
• 2 Wagner W, Reckers-Czaschka R. Oxiconazol bei Dermatomykosen – ein doppelblinder, randomisierter Therapievergleich mit Bifonazol. Mykosen 1987; 30: 484-492
• 3 Watanabe S, Takahashi H, Nishikawa T et al. A comparative clinical study between 2 weeks of luliconazole 1% cream treatment and 4 weeks of bifonazole 1% cream treatment for tinea pedis. Mycoses 2006; 49: 236-241
• 4 Massone L, Pestarino A, Borghi S et al. Treatment of erythrasma with 1 % bifonazole cream. Clin Ter 1987; 123: 105-109
• 5 Nenoff P, Haustein UF. Der Effekt antiseborrhoischer Substanzen gegenüber Pityrosporum ovale in vitro . Hautarzt 1994; 45: 464-467
• 6 Nenoff P, Haustein U-F. In vitro susceptibility testing of Pityrosporum ovale against antifungal, antiseborrheic and antipsoriatic agents. J Eur Acad Dermatol Venerol 1994; 3: 331-333
• 7 Nenoff P, Haustein U-F, Brandt W. Antifungal activity of the essential oil of Melaleuca alternifolia (tea tree oil) against pathogenic fungi in vitro . Skin Pharmacol 1996; 9: 388-394
• 8 Nenoff P. In vitro-Empfindlichkeitstestung von Malassezia furfur . Zeitschr H+G 1997; 72: 104-109
• 9 Nenoff P, Haustein UF. In vitro susceptibility testing of Malassezia furfur against rilopirox. Skin Pharmacology 1997; 10: 275-280
• 10 Nenoff P, Haustein UF. In vitro activitiy of phytosphingosines against Malassezia furfur and Candida albicans . Acta Dermato-Venereol 2002; 82: 170-173
• 11 Nenoff P, Haustein UF, Hittel N. Activity of nadifloxacin (OPC-7251), and seven other antimicrobial agents against aerobic and anaerobic bacteria isolated from bacterial skin infections. Chemotherapy 2004; 50: 196-201
• 12 Blaise G, Nikkels AF, Hermanns-Lê T et al. Corynebacterium-associated skin infections. Int J Dermatol 2008; 47: 884-890
• 13 Rho NK, Kim BJ. A corynebacterial triad: Prevalence of erythrasma and trichomycosis axillaris in soldiers with pitted keratolysis. J Am Acad Dermatol 2008; 58: 57-58
• 14 Dalal A, Likhi R. Corynebacterium minutissimum bacteremia and meningitis: a case report and review of literature. J Infect 2008; 56: 77-79
• 15 Altmeyer P. Erythrasma. In: Enzyklopädie der Dermatologie, Venerologie, Allergologie, Umweltmedizin. Berlin Heidelberg: Springer. Online-Ausgabe 2010
• 16 Hodson SB, Henslee TM, Taichibana DK et al. Interdigital erythrasma. Part I: A review of the literature. J Am Pod Med Assoc 1988; 78: 551-558
• 17 Miller SD, David-Bajar K. Images in clinical medicine. A brilliant case of erythrasma. N Engl J Med 2004; 351: 1666
• 18 Mahajan S, Koranne RV, Sharma SK. Cutaneous manifestation of diabetes mellitus. Indian J Dermatol Venereol Leprol 2003; 69: 105-108
• 19 Ahmed I, Goldstein B. Diabetes mellitus. Clin Dermatol 2006; 24: 237-246
• 20 Ruocco E, Baroni A, Donnarumma G et al. Diagnostic procedures in dermatology. Clin Dermatol 2011; 29: 548-556
• 21 Yasuma A, Ochiai T, Azuma M et al. Exogenous coproporphyrin III production by Corynebacterium aurimucosum and Microbacterium oxydans in erythrasma lesions. J Med Microbiol 2011; 60: 1038-1042
• 22 Inci M, Serarslan G, Ozer B et al. The prevalence of interdigital erythrasma in southern region of Turkey. J Eur Acad Dermatol Venereol 07.10.2011; (Epub ahead of print)
• 23 Maleki M, Fata A. Evaluation of wood’s light and direct smear for diagnosis of pityriasis versicolor and erythrasma. Saudi Med J 2005; 26: 1483-1484
• 24 Morales-Trujillo ML, Arenas R, Arroyo S. Interdigital erythrasma: clinical, epidemiologic, and microbiologic findings. Actas Dermosifiliogr 2008; 99: 469-473
• 25 Nenoff P, Krüger C. Dermatophyten-Infektionen der Haut, Haare und Nägel – klinische Aspekte – ein Update, Teil 1. Akt Dermatol 2012; im Druck
• 26 Avci O, Tanyildizi T, Kusku E. A comparison between the effectiveness of erythromycin, single-dose clarithromycin and topical fusidic acid in the treatment of erythrasma. J Dermatolog Treat 18.09.2011; (Epub ahead of print)
• 27 Macura AB. In vitro susceptibility of dermatophytes to antifungal drugs: a comparison of two methods. Int J Dermatol 1993; 32: 533-536
• 28 Berg D, Plempel M. Bifonazole, a biochemist’s view. Dermatologica 1984; 169 (Suppl. 01) 3-9
• 29 Berg D, Regel E, Harenberg HE et al. Bifonazole and clotrimazole. Arzneim-Forsch/Drug Res 1984; 34: 139-146
• 30 Hänel H, Abrams B, Dittmar W et al. A comparison of bifonazole and ciclopiroxolamine: In vitro, animal, and clinical studies. Mycoses 1988; 31: 632-640
• 31 Barug D, Bastiaanse HB. An evaluation of the antifungal effect of bifonazole on Torulopsis glabrata and Candida albicans under various in vitro test conditions. Arzneimittelforschung 1983; 33: 524-528
• 32 Camoutsis C, Geronikaki A, Ciric A et al. Sulfonamide-1,2,4-thiadiazole derivatives as antifungal and antibacterial agents: synthesis, biological evaluation, lipophilicity, and conformational studies. Chem Pharm Bull (Tokyo) 2010; 58: 160-167
• 33 Gerven FV. Odds FC. The anti-Malassezia furfur activity in vitro and in experimental dermatitis of six imidazole antifungal agents: bifonazole, clotrimazole, flutrimazole, ketoconazole, miconazole and sertaconazole. Mycoses 1995; 38: 389-393
• 34 Yamaguchi H, Uchida K. Susceptibility of clinical isolated dermatophytes to bifonazole since its launch in Japan 10 years ago. Abstract, 13th Congress of the International Society for Human and Animal Mycology. Salsomaggiore Terme, Parma, Italy, June 8 – 13, 1997
• 35 Plempel M, Regel E, Büchel KH. Antimycotic efficacy of bifonazole in vitro and in vivo . Arzneim-Forsch/Drug Res 1983; 33: 517-524
• 36 Trovato L, Rapisarda MF, Greco AM et al. In vitro susceptibility of nondermatophyte molds isolated from onycomycosis to antifungal drugs. J Chemother 2009; 21: 403-407
• 37 Karioti A, Sokovic M, Ciric A et al. Antimicrobial properties of Quercus ilex L. proanthocyanidin dimers and simple phenolics: evaluation of their synergistic activity with conventional antimicrobials and prediction of their pharmacokinetic profile. J Agric Food Chem 2011; 59: 6412-6422
• 38 El Hage S, Lajoie B, Feuillolay C et al. Synthesis, antibacterial and antifungal activities of bifonazole derivatives. Arch Pharm (Weinheim) 2011; 344: 402-410
• 39 Gupta AK, Nicol K, Batra R. Role of antifungal agents in the treatment of seborrheic dermatitis. Am J Clin Dermatol 2004; 5: 417-422
• 40 Tronnier H, Herling M, Wiebusch M et al. Untersuchungen zur antiphlogistischen Wirkung von Bifonazol. Akt Dermatol 2005; 31: 21-26
• 41 Zawar V. Photoletter to the editor: Trichomycosis (trichobacteriosis) axillaris. J Dermatol Case Rep 2011; 5: 36-37
• 42 Coyle MB, Lipsky BA. Coryneform bacteria in infectious diseases: clinical and laboratory aspects. Clin Microbiol Rev 1990; 3: 227-246
• 43 Orfanos CE, Schloesser E, Mahrle G. Hair destroying growth of Corynebacterium tenuis in the so-called trichomycosis axillaris. New findings from scanning electron microscopy. Arch Dermatol 1971; 103: 632-639
• 44 Shelley WB, Miller MA. Electron microscopy, histochemistry, and microbiology of bacterial adhesion in trichomycosis axillaris. J Am Acad Dermatol 1984; 10: 1005-1014
• 45 Darras-Vercambre S, Carpentier O, Vincent P et al. Photodynamic action of red light for treatment of erythrasma: preliminary results. Photodermatol Photoimmunol Photomed 2006; 22: 153-156