Natamycin - antimycotic of polyene macrolides class with unusual properties

Cover Page

Cite item


In the current literature review issues regarding physicochemical peculiarities, mechanism ot action and satety aspects ot polyene macrolides class compound natamycin are enlightened along with the extensive clinical data upon the use ot pharmaceuticals containing this active ingredient.

About the authors

I. O. Malova

Irkutsk State Medical University

Author for correspondence.
Russian Federation

D. D. Petrunin

Representative office ot Astellas Pharma Europe B.V

Russian Federation


  1. Kauffman C.A., Pappas P.G., Sobel J.D., Dismukes W.E. (eds). Essentials of Clinical Mycology. Second Edition. New York: Springer Science + Business Media, LLC, 2011.
  2. Reiss E., Shadomy H.J., Lyon J.M. (eds). Fundamental Medical Mycology. New Jersey: John Wiley & Sons, Inc., 2012.
  3. Kotler-Brajtburg J., Medoff G., Kobayashi G.S. et al. Classification of polyene antibiotics according to chemical structure and biological effects. Antimicrob Agents Chemother 1979; 15 (5): 716-22.
  4. Hamilton-Miller J.M. Chemistry and biology of the polyene macrolide antibiotics. Bacteriol Rev. 1973; 37 (3): 166-96.
  5. Bolard J. How do the polyene macrolide antibiotics affect the cellular membrane properties? Biochim Biophys Acta 1986; 864: 257-304.
  6. Monk B.C., Goffeau A. Outwitting multidrug resistance to antifungals. Science 2008; 321: 367-369.
  7. Kanafani Z.A., Perfect J.R. Antimicrobial resistance: Resistance to antifungal agents: Mechanisms and clinical impact. Clin Infect Dis 2008; 46: 120-128.
  8. Ghannoum M.A., Rice L.B. Antifungal agents: mode of action, mechanisms of resistance, and correlation of these mechanisms with bacterial resistance. Clin Microbiol Rev 1999; 12: 501-517.
  9. Hamilton-Miller JMT. Non-emergence of polyene-resistant yeasts: an hypothesis. Microbios 1974; 10A: 91-95.
  10. Czeizel A.E., Kazy Z., Vargha P. A case-control teratological study of vaginal natamycin treatment during pregnancy. Reproductive Toxicology 2003; 17: 387-391.
  11. Levinskas G.J., Ribelin W.E., Shaffer C.B. Acute and chronic toxicity of pimaricin. Toxicol and Appl Pharmacol 1966; 8: 97-109.
  12. Raab P.W. Natamycin (Pimaricin). Its properties and possibilities in medicine. Stuttgart: Georg Thieme Publishers, 1973; 134 p.
  13. Omura S. (ed.). Macrolide antibiotics. Chemistry, biology and practice. 2nd edition. San Diego: Elsevier Science, 2002.
  14. Woodward R.B. Struktur und Biogenese der Makrolide. Eine neue Klasse von Naturstoften. Angew Chem 1957; 69: 50-58.
  15. Masamune S., Bates G.S., Corcoran J.W. Macrolides. Recent progress in chemistry and biochemistry. Angew Chem Int Edit Engl 1977; 16: 585-607
  16. Dutcher J.D. 1968. Polyene antibiotics, p.133- 143. Kirk-Othmer Encyclopedia of Chemical Technology, vol. 16
  17. Lampen J.O. Amphotericin B and other polyenic antifungal antibiotics. Amer J Clin Pathol 1969; 52: 138-146.
  18. Neelameghan A. Physico-chemical data on antibiotics. II (1). Hindustan Antibiot Bull 1960; 2: 131-155.
  19. Oroshnik W., Mebane A.D. The polyene antifungal antibiotics. Prog Chem Org Nat Prod 1963; 21: 17-79.
  20. Vining L.C. The polyene antifungal antibiotics. Hindustan Antibiot Bull 1960; 3: 37-54.
  21. Waksman S.A. The actinomyces and their antibiotics. Advan Appl Microbiol 1963; 5: 235-315.
  22. Aizawa S., Shibuya M., Shirato S. Resistaphylin, a new antibiotic. I. Production, isolation and properties. J Antibiot 1971; 24: 393-396.
  23. Coronelli C., Pasqualucci R.C., Thiemann J.E., Tamoni G. Mycotrienin, a new polyene antibiotic isolated from Streptomyces. J Antibiot 1967; 20A: 329-333.
  24. Neseman G., Prave P., Sukatsch D., Vertesy L. Ein Polyen-Antibiotikum aus Bakterien. Naturwissenschaften 1972; 59: 81-82.
  25. Vertesy L. Proticin, a new phosphorus-containing antibiotic. II. Characterization and chemical studies. J Antibiot 1972; 25: 4-10.
  26. Arishima M., Sakamoto J. Cryptocidin, an antibiotic substance. Japanese Patent 1960; 13897 (60).
  27. Kuroya M. Antibiotic substance, flavacid. Japanese Patent 1954; 8547 (54).
  28. Narasimhachari N., Swami M.B. Dermostatin: a revised hexaene structure. J Antibiot 1970; 23: 566.
  29. Sakamoto JMJ. Etude sur antibiotique antifongique. II. La cryptocidine, un nouvel antibiotique produit par les Streptomycetes. J Antibiot 1959; 12A: 21-23.
  30. Takahashi I. A new antifungal substance, flavacid. J Antibiot 1953; 6A: 1177121.
  31. Thirumalachar M.J., Menon S.K. Dermostatin. a new antifungal agent. I. Microbiological studies. Hindustan Antibiot Bull 1962; 4: 106-108.
  32. Arcamone F., Bertazzoli C., Canevazzi G. et al. La etruscomicina, nuova antibiotico produtto dallo Streptomyces lucensis sp. nov. Giorn Microbiol 1957; 4: 119-128.
  33. Chong C.N., Rickards R.W. Macrolide antibiotic studies. XVI. The structure of nystatin. Tetrahedron Lett 1970; № 59: 5145-5148.
  34. Gold W., Stout H.A., Pagano J.F., Donovick R. Amphotericins A and B, antifungal antibiotics produced by a streptomycete. I. In vitro studies, p. 579-586. Antibiot Ann 1955-1956: 579-586.
  35. Struyk A.P., Hoette I., Drost G. et al. Pimaricin, a new antifungal antibiotic. Antibiot Ann 1957- 1958: 878-884.
  36. Vandeputte J., Wachtel J.L., Stiller E.T. Amphotericins A and B. antifungal antibiotics produced by a streptomycete. II. The isolation and properties of the crystalline amphotericins. Antibiot Ann 1955-1956: 587-591.
  37. Gopalkrishnan K.S., Narasimhachari N., Joshi V.B., Thirumalachar M.J. Chainin: a new methylpentaene antibiotic from a species of Chainia. Nature (London) 1968; 218: 597-598.
  38. Ogawa H., Ito T., Inoue S., Nishio M. Chemical study of moldcidin B and its identification with pentamycin. J Antibiot 1960; 13A: 353-355.
  39. Pandey R.C., Rinehart K.L. Polyene antibiotics. V. Characterization of components of the Filipin complex. J. Antibiot 1970; 23: 414-417.
  40. Pandey R.C., Narasimhachari N., Rinehart K.L., Millington D.S. Polyene antibiotics. IV. The structure of chainin. J Amer Chem Soc 1972; 94: 4306-4310.
  41. Umezawa S., Tanaka Y., Ooka M., Shiotsu S. A new antifungal antibiotic, pentamycin. J Antibiot 1958; 11A: 26-29.
  42. Whitfield G.B., Brock T.D., Amman A. et al. Filipin. An antifungal antibiotic: isolation and properties. J Amer Chem Soc 1955; 77: 4799-4801.
  43. Borowski E., Malyshkina M., Soloviev S., Ziminski T. Isolation and characterization of levorin A and B, the heptaenic macrolide antifungal antibiotics of aromatic subgroup. Chemotherapia 1965/66; 10: 176-194.
  44. Deshpande G.R., Kerur D.R., Narasimhachari N. Chemical studies on hamycin. I. Purification, counter-current distribution and chemical degradation. Hindustan Antibiot Bull 1966; 8: 185-193.
  45. Hattori K. Studies on trichomycin. VIII. Chemical structure of trichomycin. J Antibiot 1962; 15B: 39-43.
  46. Hosoya S., Komatsu N., Soeda M. et al. Trichomycin, a new antibiotic with trichomonadicidal and antifungal activities. J Antibiot 1952; 5: 566.
  47. Lee C.H., Schaffner C.P. Perimycin. The structure of some degradation products. Tetrahedron 1969; 25: 2229-2232.
  48. Mechlinski W., Schaffner C.P., Ganis P., Avitabile G. Structure and absolute configuration of the polyene macrolide antibiotic amphotericin B. Tetrahedron Lett 1970; No.44: 3873-3876.
  49. Thirumalachar M.J., Menon S.K., Bhatt V.V. Hamycin. I. Discovery and biological studies. Hindustan Antibiot Bull 1961; 3: 136-138.
  50. Burns J., Holtman D.F. Tennecetin: a new antifungal antibiotic; general characteristics. Antib Chemother 1959; 9: 398.
  51. Divekar P.V., Bloomer J.L., Eastham J.F. et al. The isolation of crystalline tennecetin and the comparison of this antibiotic with pimaricin. Antib Chemother 1961; 11: 377.
  52. Welsh A.L. Tennecetin. Ann NY Acad Sci 1960; 89: 267.
  53. Clark W.L., Shirk R.J., Kline E.F. Pimaricin, a new food fungistat. In "microbial inhibitors in food”. (ed. Molin N) 167-184, Alqvist & Wiksell, Uppsala, 1964.
  54. European Directive 95/2/EC on food additives other than colours and sweeteners.
  55. Patrick J.B., Williams R.P., Wolf C.F., Webb J.S. Pimaricin II. The structure of pimaricin. J Amer Chem Soc 1958; 80: 6689.
  56. Ceder O. Pimaricin IV. Complete structure of the antibiotic. Acta Chem Scand 1964; 18: 126.
  57. Ceder O., Hansson B. Pimaricin VII. The absolute configuration at C-25. Tetrahydron 1967; 23: 3753.
  58. Golding B.T., Rickards R.W., Meyer W.E. et al. The structure of the macrolide antibiotic pimaricin. Tetrahydron Lett 1956; 30: 3551-3557.
  59. Gaudiano G., Bravo P., Mauri G. Lucensomicina e pimaricina: determinazione della configurazione alloluta dell’atomo di carbonio su cui si chiude l’anello lattonico. Chim Ind 1966; 48: 1327.
  60. Porter J.N., Wilhelm J.J., Tresner H.D. Method for the preferential isolation of actynomycetes from soil. Appl Microbiol 1960; 8: 174.
  61. Dekker J., Ark P.A. Protection of the antibiotic pimaricin from oxidation and ultraviolet light by chlorophyllin and other compounds. Antib Chemother 1959; 9: 327.
  62. Posthuma J., Berends W. Energy transfer in aqueous solutions. Biochim Biophys Acta 1965; 51: 392.
  63. Lynch H.J., Furcolow M.L., Yates J.L. et al. Toxicity and absorption studies in humans of newer antifungal agents. Antimicrob Agents Annual 1960: 51.
  64. Newcomer V.D., Sternberg T.H., Wright E.T. et al. The treatment of systemic mycoses with orally administered pimaricin: preliminary report. Ann N Y Acad Sci 1960; 89: 240-6.
  65. Manten A., Hoogerheide J.C. The influence of a new antifungal antibiotic, pimaricin, on the yeast flora of the gastrointestinal tract of rats and mice during tetracycline administration. Antibiot Chemother (Northfield III) 1958; 8 (8): 381-6.
  66. Lindh H.F. A method for evaluation of antifungal drugs against enteric Candida albicans in mice. Antibiot Chemother (Northfield III) 1959; 9 (4): 226-31.
  67. Drouhet E. Experimental study of a new antifungal antibiotic, pimaricin. Bull Soc Fr Dermatol Syphiligr 1965; 72 (3): 249-53. French.
  68. Draize J.H., Kelley E.A. Surface active agents and the eye. Drug Cosmetic Ind 1952; 71: 36- 37, 118-120.
  69. Korteweg G.C., Szabo K.L., Rutten A.M., Hoogerheide J.C. Some pharmacological properties of Pimaricin and possible clinical application of this antifungal antibiotic. Antibiot Chemother 1963; 11: 261-72.
  70. Arora H.R. A study on the effects of pentamycin and pimaricin, two polyene antifungal antibiotics on the guinea pig heart. Med Pharmacol Exp Int J Exp Med 1965; 12: 239-44.
  71. Johansen J.D., Frosch P.J., Lepoittevin J.P. (eds.) Contact Dermatitis. 5th ed. SpringerVerlag Berlin Heidelberg 2011; 1262 p.
  72. Nosbaum A., Vocanson M., Rozieres A. et al. Allergic and irritant contact dermatitis. Pathophysiology and immunological diagnosis. Eur J Dermatol 2009; 19 (4): 325-32.
  73. Malten K.E. (1968) Report on investigation into possible sensitising side effects of pimaricin in human beings. Unpublished report from the Instituut voor Geneeskunde en Maatschappij, Nijmegen. Submitted to WHO by Gist-Broades NV, Delft.
  74. Mattia A., Cerniglia C., Baines J. Safety evaluation of certain food additives and contaminants. Natamycin (pimaricin). WHO Food Additives Series, No. 48, 2001.
  75. Kligman A.M., Epstein W. Updating the maximization test for identifying contact allergens. Contact Dermatitis 1975; 1: 231-239.
  76. Cox G.E., Bailey D.E., Morgareidge K. (1973) Unpublished report No. 1-1052 submitted to WHO by Food and Drug Research Laboratories Inc.
  77. Bailey D.E., Morgareidge K. (1974) Teratogenicity test with pimaricin. Unpublished report No. 1-1052 submitted to WHO by Food and Drug Research Laboratories Inc.
  78. De Kruijff B., Demel R.A. Polyene antibiotic-sterol interactions in membranes of Achole-plasma laidlawii cells and lecithin liposomes. III. Molecular structure of the polyene antibioticcholesterol complexes. Biochim Biophys Acta 1974; 339: 57-70.
  79. Mysyakina I.S., Funtikova N.S. The role of sterols in morphogenetic processes and dimorphism in fungi. Microbiology 2007; 76: 1-13.
  80. Heese-Peck A., Pichler H., Zanolari B. et al. Multiple functions of sterols in yeast endocytosis. Mol Biol Cell 2002; 13: 2664-2680.
  81. Kato M., Wickner W. Ergosterol is required for the Sec18 / ATP-dependent priming step of homotypic vacuole fusion. EMBO J 2001; 20: 4035-4040.
  82. Takeshita N., Higashitsuji Y., Konzack S., Fischer R. Apical sterol-rich membranes are essential for localizing cell end markers that determine growth directionality in the filamentous fungus Aspergillus nidulans. Mol Biol Cell 2008; 19, 339-351.
  83. Baginski M., Resat H., McCammon J.A. Molecular properties of amphotericin B membrane channel: a molecular dynamics simulation. Mol Pharmacol 1997; 52: 560-570.
  84. te Welscher Y.M., ten Napel H.H., Masia Balague M. et al. Natamycin blocks fungal growth by binding specifically to ergosterol without permeabilizing the membrane. J Biol Chem 2008; 283: 6393-6401.
  85. te Welscher Y.M., Jones L., van Leeuwen M.R. et al. Natamycin inhibits vacuole fusion at the priming phase via a specific interaction with ergosterol. Antimicrob Agents Chemother 2010; 54 (6): 2618-25.
  86. Brown D.A., London E. Functions of lipid rafts in biological membranes. Annu Rev Cell Dev Biol 1998; 14: 111-136.
  87. Rodriguez R.J., Low C., Bottema C.D., Parks L.W. Multiple functions for sterols in Saccharomyces cerevisiae. Biochim Biophys Acta 1985; 837: 336-343.
  88. Simons K., Ikonen E. Functional rafts in cell membranes. Nature 1997; 387: 569-572.
  89. D’Hondt K., Heese-Peck A., Riezman H. Protein and lipid requirements for endocytosis. Annu Rev Genet 2000; 34: 255-295.
  90. Salaun C., James D.J., Chamberlain L.H. Lipid rafts and the regulation of exocytosis. Traffic 2004; 5: 255-264.
  91. Kato M., Wickner W. Ergosterol is required for the Sec18/ATP-dependent priming step of homotypic vacuole fusion. EMBO J 2001; 20: 4035-4040.
  92. Wickner W. Yeast vacuoles and membrane fusion pathways. EMBO J 2002; 21: 1241-1247.
  93. van Leeuwen M.R., Golovina E.A., Dijksterhuis J. The polyene antimycotics nystatin and filipin disrupt the plasma membrane, whereas natamycin inhibits endocytosis in germinating conidia of Penicillium discolor. J Appl Microbiol. 2009; 106 (6): 1908-18.
  94. van Leeuwen M.R., Krijgsheld P., Wyatt T.T. et al. The effect of natamycin on the transcriptome of conidia of Aspergillus niger. Stud Mycol. 2013; 74 (1): 71-85.
  95. te Welscher Y.M., van Leeuwen M.R., de Kruijff B. et al. Polyene antibiotic that inhibits membrane transport proteins. Proc Natl Acad Sci U S A. 2012; 109 (28): 11156-9.
  96. Gray K.C., Palacios D.S., Dailey I. et al. Amphotericin primarily kills yeast by simply binding ergosterol. Proc Natl Acad Sci USA 2012; 109: 2234-2239.
  97. Hopsu-Havu V.K., Nevalainen T.J. Electron microscopic observations on natamycin effect in Candida albicans cell wall. Mykosen. 1979 Oct; 22 (10): 364-70.
  98. Raab P.W. Pharmacology and clinical pharmacology of natamycin (pimaricin). Castellania 1973; 1 (6): 179-181.
  99. Holt R.J., Newman R.L. Candida in the faeces of children receiving oral tetracycline and phenoxymethyl penicillin. J Clin Pathol. 1967; 20 (1): 80-3.
  100. Marselou-Kinti U. Sensitivity of blastomycetes of the Candida genus to pimaricin. Bull Greek Soc Microbiol Hygiene 1968; 2: 85.
  101. Porebska A., Laskownicka Z., Zemburowa K. Fungostatic activity in vitro of the new antibiotic-pimaricin (natamycin). Med Dosw Mikrobiol 1971; 23 (1): 71-6. Polish
  102. Asami K., Shintaku A., Kawamjra N. Effect of an anti-fungal agent, Pimaricin, on Trichomonas vaginalis in vitro. J Antibiot B 1967; 20 (5): 344-6. Japanese.
  103. Naranjo P. Treatment of some intestinal protozooses with trichomycin and pimaricin. Chemotherapia (Basel). 1961; 3: 532-43. German.
  104. Perlman D. Antibiotic inhibition of algal growth. Antimicrob Agents Chemother (Bethesda) 1964; 10: 114-9.
  105. Seok J.Y., Lee Y., Lee H. et al. Human cutaneous protothecosis: report of a case and literature review. Korean J Pathol. 2013; 47 (6): 575-8.
  106. Lass-Flörl C, Mayr A. Human protothecosis. Clin Microbiol Rev. 2007; 20 (2): 230-42.
  107. Tsao P.H., Thieleke D.W. Stimulation of bacteria and actinomycetes by the polyene antibiotic pimaricin in soil dilution plates. Can J Microbiol. 1966; 12 (6): 1091-4.
  108. Morschhauser J. The genetic basis of fluconazole resistance development in Candida albicans. Biochim Biophys Acta 2002; 1587: 240-248.
  109. Cernicka J., Subik J. Resistance mechanisms in fluconazole-resistant Candida albicans isolates from vaginal candidiasis. Int J Antimicrob Agents 2006; 27: 403-408.
  110. Malbahova E.T., Arzumanjan V.G., Komissarova L.M., Karapetjan T.Je. Vulvovaginal candidiasis: species diversity and sensitivity to antimycotic agents. Akusherstvo i Ginekologija 2009; 4: 44-46. [Мальбахова Е.Т., Арзуманян В.Г., Комиссарова Л.М., Карапетян Т.Э. Вульвовагинальный кандидоз: видовое разнообразие и чувствительность к противогрибковым препаратам. Акушерство и гинекология 2009; (4): 44-46.]
  111. Bulik C.C., Sobel J.D., Nailor M.D. Susceptibility profile of vaginal isolates of Candida albicans prior to and following fluconazole introduction - impact of two decades. Mycoses. 2011; 54 (1): 34-8.
  112. Asticcioli S., Sacco L., Daturi R. et al. Trends in frequency and in vitro antifungal susceptibility patterns of Candida isolates from women attending the STD outpatients clinic of a tertiary care hospital in Northern Italy during the years 2002-2007. New Microbiol 2009; 32 (2): 199-204.
  113. Veselov A.V., Multyh I.G., Kljasova G.A., Agapova E.D. et al. Epidemiology of candidiasis causative agents and their sensitivity to azoles - results of ARTEMIS Disk trial in Russia. Klinicheskaja Mikrobiologija i Antimikrobnaja Himioterapija 2005; 7 (1): 68-76. [Веселов А.В., Мултых И.Г., Клясова Г.А., Агапова Е.Д. и соавт. Эпидемиология возбудителей кандидозов и их чувствительность к азолам: результаты исследования ARTEMIS Disk в России. Клин микробиол и антимикр химиотер 2005; 7 (1): 68-76.]
  114. Richter S.S., Galask R.P., Messer S.A. et al. Antifungal susceptibilities of Candida species causing vulvovaginitis and epidemiology of recurrent cases. J Clin Microbiol 2005; 43 (5): 2155-62.
  115. Balkis M.M., Leidich S.D., Mukherjee P.K., Ghannoum M.A. Mechanisms of fungal resistance. An overview. Drugs 2002; 62 (7): 125-140.
  116. Molzahn S.W., Woods R.A. Polyene resistance and the isolation of sterol mutants in Saccharomyces cerevisiae. J Gen Microbiol 1972; 72: 339-348.
  117. Dick J.D., Merz W.G., Saral R. Incidence of polyene-resistant yeasts recovered from clinical specimens. Antimicrob Agents Chemother 1980; 18: 158-163.
  118. Safe L.M., Safe S.H., Subden R.E., Morris D.C. Sterol content and polyene antibiotic resistance in isolates of Candida krusei, Candida parakrusei, and Candida tropicalis. Can J Microbiol 1977; 23 (4): 398-401.
  119. Subden R.E., Safe L., Morris D.C. et al. Eburicol, lichesterol, ergosterol, and obtusifoliol from polyene antibiotic-resistant mutants of Candida albicans. Can J Microbiol 1977; 23 (6): 751-4.
  120. Jin H., McCaffery J.M., Grote E. Ergosterol promotes pheromone signaling and plasma membrane fusion in mating yeast. J Cell Biol 2008; 180: 813-826.
  121. Munn A.L., Heese-Peck A., Stevenson B.J. et al. Specific sterols required for the internalization step of endocytosis in yeast. Mol Biol Cell 1999; 10: 3943-3957.
  122. Pimafucin (vaginal suppositories) product labeling P № 013552/01 from 07.06.2011. [Инструкция по медицинскому применению препарата Пимафуцин (суппозитории вагинальные) П № 013552/01 от 07.06.2011].
  123. Pimafucin (cream for topical application) product labeling P № 013552/02 from 09.10.2008. [Инструкция по медицинскому применению препарата Пимафуцин (крем для наружного применения) П № 013552/02 от 09.10.2008.]
  124. Pimafucort (cream and ointment for topical application) product labeling P № 012689/01 and P № 012689/01 from 01.07.2009. [Инструкция по медицинскому применению препарата Пимафукорт (крем и мазь для наружного применения) П № 012689/01 и П № 012689/01 от 01.07.2009.]
  125. Pimafucin (enteric-coated tablets) product labeling P № 013552/03 from 03.03.2009. [Инструкция по медицинскому применению препарата Пимафуцин (таблетки, покрытые кишечно-растворимой оболочкой) П № 013552/03 от 03.03.2009.]
  126. FlorCruz N.V., Peczon I.V., Evans J.R. Medical interventions for fungal keratitis. Cochrane Database Syst Rev. 2012 Feb 15; 2: CD004241.
  127. Primafungin (vaginal suppositories) product labeling LP-000411 from 28.02.2011. [Инструкция по медицинскому применению препарата Примафунгин (суппозитории вагинальные) ЛП-000411 от 28.02.2011.]
  128. Ecofucin (vaginal suppositories) product labeling LP-002341 from 13.01.2014. [Инструкция по медицинскому применению препарата Экофуцин (суппозитории вагинальные) ЛП-002341 от 13.01.2014.]
  129. Wiedey K.D., Kompa H.E., Franz H. Dosiswirkungs mit dem polyenantimykotikum Natamycin in einem galenish neu entwickelten Ovulum bei vaginalen Hefeinfektionen. Mycosen 1984; 27 (8): 415-420.
  130. Vartiainen E., Widholm O. A single-blind, group-comparative study to compare the efficacy of Pimafucin 100 mg ovules and Gyno-Daktarin 400 mg vaginal capsules in the treatment of vulvovaginal candidiasis. Gist-Brocades Documentation 1987; № 451: 1-16
  131. Koch J. Lokalbehandlung von Vaginalmykosen. Der Algemeinarzt 1987; 7: 460-465. German.
  132. Kretowitz J., Troszynski M. Skutecznosc nowej formy leku przeciwgrzybiczego Pimafucin (natamycin) globulek dopochwowych oraz porownanie ich z Pimafucin tabletkami dopochwowymi. Ginekologia Polska 1990; 61 (8): 417-422. Polish.
  133. Tóth B., Palos H. [Therapeutic results achieved through the advantage of a combination of oral metronidazole and vaginal natamycin tablets in urogenital protozoan, trichobacterial and blastomyces infections]. Zentralbl Gynakol. 1975; 97 (13): 816-22. German
  134. Prilepskaja V.N., Pikuza V.V. Use of Pimafucin in treatment of vaginal candidiasis. Klinicheskaja farmakologija i terapija 1994; 3: 85. [Прилепская В.Н., Пикуза В.В. Применение Пимафуцина в лечении вагинального кандидоза. Клин фармакол терап 1994; (3): 85.]
  135. Patel V.R. Natamycin in the treatment of vaginal candidiasis in pregnancy. Practitioner 1973; 210 (259): 701-3.
  136. Basile F. [Use of pimaricin in the therapy of mycotic-protozoal vulvovaginitis]. Minerva Ginecol. 1970; 22 (11): 584-7. Italian.

Copyright (c) 2015 Malova I.O., Petrunin D.D.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 60448 от 30.12.2014.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies