Scientific letter
Treatment of refractory Candida krusei vaginitis with topical amphotericin B
Tratamiento de la vaginitis refractaria por Candida krusei con anfotericina B tópica
Esther Chamorro-de-Vega
, Maria-Victoria Gil-Navarro, Jose-Luis Perez-Blanco
Corresponding author
Departamento de Farmacia, Hospital Virgen del Rocío, Sevilla, Spain
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The increased use of vaginal cultures in the treatment of women with chronic recurrent or relapsing vaginitis has provided clinicians with new insights of the different <span class="elsevierStyleItalic">Candida</span> species that are responsible for yeast vaginitis. <span class="elsevierStyleItalic">Candida krusei</span> is a very unusual cause of fungal vaginitis (0.7% of cases). Several investigators have questioned whether it is a true vaginal pathogen.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Conventional antimycotic treatments are less active in vitro against <span class="elsevierStyleItalic">Candida non-albicans</span> than against <span class="elsevierStyleItalic">Candida albicans</span>. <span class="elsevierStyleItalic">C. krusei</span> is usually resistant to fluconazol, but is likely to respond to oral itraconazole or ketoconazole. Voriconazol and itraconazole also have demonstrated favorable in vitro antifungal activity but they are not available as topical preparations.</p><p id="par0015" class="elsevierStylePara elsevierViewall">We describe a case of persistent vaginal candidiasis due to <span class="elsevierStyleItalic">C. krusei</span>, unresponsive to conventional antifungal therapy.</p><p id="par0020" class="elsevierStylePara elsevierViewall">A 61-year-old woman, with no family history of interest, recipient of a kidney transplant 10 years ago, diagnosed with transplant glomerulopathy with potent immunosuppression, presented with vulvo-vaginitis with vaginal culture isolation of <span class="elsevierStyleItalic">C. krusei</span>. The patient has also proteinuria and urine isolation of <span class="elsevierStyleItalic">Escherichia coli</span>. She was treated with 400<span class="elsevierStyleHsp" style=""></span>mg ovule of ketoconazol once daily for 4 days and fosfomicine 500<span class="elsevierStyleHsp" style=""></span>mg once daily for 3 days. Twenty days later, the patient came to the physician's office with an injury in labia majora. The vaginal culture remained positive for <span class="elsevierStyleItalic">C. krusei</span>, with higher proportion of yeast than in the previous culture. Just before the vulvo-vaginitis, the patient had presented a recurrent <span class="elsevierStyleItalic">E. coli</span> UTI treated with cephalosporins and 45 days just prior to the genital ulcer, had had <span class="elsevierStyleItalic">Clostridium difficile</span> diarrhea for which he was effectively treated with oral metronidazole for 10 days.</p><p id="par0025" class="elsevierStylePara elsevierViewall">An exhaustive search of the literature published on the treatment of this type of candidiasis was conducted. As a result, we found that the bibliography on <span class="elsevierStyleItalic">C. krusei</span> vaginitis and its treatment was sparse, with only some case reports of refractory vulvo-vaginal candidiasis by <span class="elsevierStyleItalic">C. glabrata</span> and <span class="elsevierStyleItalic">C. krusei</span> treated topically with amphotericin alone, or in combination with flucytosine.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">2–5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">At that moment a topical formulation of amphotericin 3% for vaginal application was developed by combining amphotericin B deoxicolate with lubricanting jelly Aquagel<span class="elsevierStyleSup">®</span>. Propyleneglycol was used for lubricant incorporation. This preparation has an unknown shelf life and is obtainable from the Manufacturing Pharmacy Unit. Intravaginal formulation was given daily for 14 days.</p><p id="par0035" class="elsevierStylePara elsevierViewall">One month after, the patient had resolved her symptoms but continued to be colonized by <span class="elsevierStyleItalic">C. krusei</span>. Repeated exposure to antifungals drug over a prolonged period of time may cause a shift in the vaginal mycoflora for the more drug-susceptible <span class="elsevierStyleItalic">C. albicans</span> to the less drug-susceptible candida species, such as <span class="elsevierStyleItalic">C. krusei</span>.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Despite the vaginal cultures remained positive, the symptoms were resolved, showing that amphotericin in lubricating jelly may be an effective option to treat symptomatic <span class="elsevierStyleItalic">C. krusei</span> vulvo-vaginitis where conventional azole therapy has failed. This topical formulation has emerged as a potential effective treatment but is not widely available and more studies are needed to set the optimal posology.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Chamorro-de-Vega E, Gil-Navarro M-V, Perez-Blanco J-L. Tratamiento de la vaginitis refractaria por <span class="elsevierStyleItalic">Candida krusei</span> con anfotericina B tópica. 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Vázquez" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1086/343826" "Revista" => array:6 [ "tituloSerie" => "Clin Infect Dis" "fecha" => "2002" "volumen" => "35" "paginaInicial" => "1066" "paginaFinal" => "1070" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12384840" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treatment of vaginitis caused by <span class="elsevierStyleItalic">Candida glabrata</span>: use of topical boric acid and flucytosine" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J.D. Sobel" 1 => "W. Chaim" 2 => "V. Nagappan" 3 => "D. 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