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Azole resistant Candida glabrata vulvovaginitis treated with boric acid
112
Letters to the Editor / European Journal of Obstetrics & Gynecology and Reproductive Biology 147 (2009) 111–115
*Corresponding author at: Department of Obstetrics, and Gynecology, Hadassah Ein-Kerem Medical Center, P.O. BOX 12000, Jerusalem 91120, Israel. Tel.: +972 2 6776424; fax: +972 2 6433337 E-mail address: [email protected] (H.Y. Sela) 23 January 2009 doi:10.1016/j.ejogrb.2009.06.017
Azole resistant Candida glabrata vulvovaginitis treated with boric acid Dear Editor, We report the case of a 27-year-old woman suffering from dyspareunya and severe vulvovaginal pruritus and burning. She was otherwise healthy, but had a history of recent administration of oral amoxicillin–clavulanate, due to acute tonsillitis. At vulvovaginal examination, erythema and discharge were observed. She was unsuccessfully treated with empirical oral fluconazole (150 mg, oral 1-day therapy). Hence, itraconazole (200 mg, every 24 h, for 3 days) was administered without success. Swabs were then taken for culture. Also, pH was 4.5, amine test was negative, whereas Gram staining showed numerous budding yeast cells and leukocytes. Candida glabrata (105 CFU/plate) was grown as a single organism. It was identified by using the bioMe´rieux Vitek2 system; susceptibilities were instead provided by an E-test method, so that the yeast showed resistance to both fluconazole (MIC 64 mg/ml) and itraconazole (MIC 1 mg/ml). The patient made a full recovery after boric acid treatment (600-mg capsule inserted intravaginally once daily for 14 days). Two-third of women have at least one episode of vulvovaginal candidiasis (VVC) during life and several females develop recurrent or chronic VVC. Though the prevalence of infections by non-Candida yeasts (such as Saccharomyces cerevisiae) is increasing, many non-albicans vaginitis are due to C. glabrata, especially in pregnant and diabetic patients. This organism often exerts resistance to azoles and polyenes. Particularly, fluconazole resistance by this yeast is due to increased ergosterol synthesis and higher expression of azole efflux pumps. In addition, diabetic patients have been known to poorly respond to single 150-mg oral doses of fluconazole. Moreover, C. glabrata shows low sensitivity to beta-defensis (if compared to C. albicans); these are natural antimicrobial/antifungal epithelial peptides, the expression of which is reduced in diabetic women. This may perhaps explain the elevated prevalence of C. glabrata candidiasis in this group of patients [1–3]. The case we reported underlines the uncommon isolation of non-albicans species among non-nosocomial patients. Further, using empirical azoles against yeasts exerting resistance may bring to antifungal failure. Boric acid (or boracic) is a weak acid; mechanism on which its activity is based still remains unclear. Anyway, it can be a valid therapeutic option versus both C. albicans and non-albicans yeasts; nevertheless, its usefulness is often underestimated, unfortunately. Boracic is known to be safe, except for occasional local burning and vestibular erythema. Particularly, diabetic female patients with C. glabrata VVC frequently respond poorly to azoles, so that topic boracic should be considered as a promising alternative. Previous works have described the better response to this compound compared with topical miconazole and nystatin in non-diabetic patients. Conversely, boric acid should not be always used as first line treatment, given that C. albicans does
not respond to this compound as good as C. glabrata [1–4,5]. Even if the patient we followed showed no alteration of glucose metabolism, we would suggest to always screen patients with genital C. non-albicans infections for diabetes. Given that clinical signs and symptoms in patients with C. albicans and C. glabrata infections is quite similar, gynecological and microbiological examinations should be carried out when a recurrent VVC develops (rather than treating it empirically), to exclude lower genital tract conditions (such as vulvar contact dermatitis, vulvar vestibulitis, vulvar neoplasia, lichen simplex chronicus), or confirm the VVC and subsequently test antifungal susceptibility of C. albicans and C. non-albicans isolates. Unfortunately, in vitro fungal susceptibility and clinical response to therapy do not always match. This may be due to several reasons, including in vivo biofilm formation on mucosal surfaces and local immunological factors predisposing to yeast infections. Nevertheless, species misidentification and lack of susceptibility data may lead to widespread and inappropriate use and self-use of antifungals, as well as long-term therapies and repeated treatments; this can finally result in selection of species (such as C. glabrata) exerting resistance to commonly used drugs. References [1] Savini V, Catavitello C, Manna A, et al. Two cases of vaginitis caused by itraconazole-resistant Saccharomyces cerevisiae and a review of recently published studies. Mycopathologia 2008;166(1):47–50. [2] Ribeiro MA, Dietze R, Paula CR, Da Matta DA, Colombo AL. Susceptibility profile of vaginal yeast isolates from Brazil. Mycopathologia 2000;151:5–10. [3] Khan ZU, Ahmad S, Al-Obaid I, Al-Sweih NA, Joseph L, Farhat D. Emergence of resistance to amphotericin B and triazoles in Candida glabrata vaginal isolates in a case of recurrent vaginitis. J Chemother 2008;20(4):488–91. [4] Ray D, Goswami R, Banarjee U, et al. Prevalence of Candida glabrata and its response to boric acid vaginal suppositories in comparison with oral fluconazole in patients with diabetes and vulvovaginal candidiasis. Diab care 2007;30(2):312–7. [5] Vermitsky JP, Edlind TD. Azole resistance in Candida glabrata: coordinate upregulation of multidrug transporters and evidence for a Pdr1-like transcription factor. Antimicrob Agents Chemother 2004;48:3773–81.
Vincenzo Savinia,*, Chiara Catavitelloa, Azaira Biancoa, Andrea Balbinota, Francesco D’Antoniob, Domenico D’Antonioa a Clinical Microbiology and Virology Unit, Department of Transfusion Medicine, ‘Spirito Santo’ Hospital, via Fonte Romana 8, CAP 65100, Pescara (Pe), Italy b Department of Gynecology, ‘SS. Annunziata’ Hospital, Chieti, Italy *Corresponding author. Tel.: +39 320 6265740 E-mail address: [email protected] (V. Savini) 27 April 2009 doi:10.1016/j.ejogrb.2009.06.020
Absolute shortness of the umbilical cord and hypoplasia of the ¨ lliker-Fuse complex arcuate nucleus and of the parabrachial/Ko in a case of sudden intrauterine fetal death Dear Editor, We report a case of sudden unexplained late fetal death at 41 + 4 gestational weeks, following physiological pregnancy, in which an absolute shortness of the umbilical cord was observed in association with developmental alterations of vital centers of the brainstem. Late fetal death or stillbirth is the death prior to the complete expulsion or extraction from the mother of a product of
Letters to the Editor / European Journal of Obstetrics & Gynecology and Reproductive Biology 147 (2009) 111–115
*Corresponding author at: Department of Obstetrics, and Gynecology, Hadassah Ein-Kerem Medical Center, P.O. BOX 12000, Jerusalem 91120, Israel. Tel.: +972 2 6776424; fax: +972 2 6433337 E-mail address: [email protected] (H.Y. Sela) 23 January 2009 doi:10.1016/j.ejogrb.2009.06.017
Azole resistant Candida glabrata vulvovaginitis treated with boric acid Dear Editor, We report the case of a 27-year-old woman suffering from dyspareunya and severe vulvovaginal pruritus and burning. She was otherwise healthy, but had a history of recent administration of oral amoxicillin–clavulanate, due to acute tonsillitis. At vulvovaginal examination, erythema and discharge were observed. She was unsuccessfully treated with empirical oral fluconazole (150 mg, oral 1-day therapy). Hence, itraconazole (200 mg, every 24 h, for 3 days) was administered without success. Swabs were then taken for culture. Also, pH was 4.5, amine test was negative, whereas Gram staining showed numerous budding yeast cells and leukocytes. Candida glabrata (105 CFU/plate) was grown as a single organism. It was identified by using the bioMe´rieux Vitek2 system; susceptibilities were instead provided by an E-test method, so that the yeast showed resistance to both fluconazole (MIC 64 mg/ml) and itraconazole (MIC 1 mg/ml). The patient made a full recovery after boric acid treatment (600-mg capsule inserted intravaginally once daily for 14 days). Two-third of women have at least one episode of vulvovaginal candidiasis (VVC) during life and several females develop recurrent or chronic VVC. Though the prevalence of infections by non-Candida yeasts (such as Saccharomyces cerevisiae) is increasing, many non-albicans vaginitis are due to C. glabrata, especially in pregnant and diabetic patients. This organism often exerts resistance to azoles and polyenes. Particularly, fluconazole resistance by this yeast is due to increased ergosterol synthesis and higher expression of azole efflux pumps. In addition, diabetic patients have been known to poorly respond to single 150-mg oral doses of fluconazole. Moreover, C. glabrata shows low sensitivity to beta-defensis (if compared to C. albicans); these are natural antimicrobial/antifungal epithelial peptides, the expression of which is reduced in diabetic women. This may perhaps explain the elevated prevalence of C. glabrata candidiasis in this group of patients [1–3]. The case we reported underlines the uncommon isolation of non-albicans species among non-nosocomial patients. Further, using empirical azoles against yeasts exerting resistance may bring to antifungal failure. Boric acid (or boracic) is a weak acid; mechanism on which its activity is based still remains unclear. Anyway, it can be a valid therapeutic option versus both C. albicans and non-albicans yeasts; nevertheless, its usefulness is often underestimated, unfortunately. Boracic is known to be safe, except for occasional local burning and vestibular erythema. Particularly, diabetic female patients with C. glabrata VVC frequently respond poorly to azoles, so that topic boracic should be considered as a promising alternative. Previous works have described the better response to this compound compared with topical miconazole and nystatin in non-diabetic patients. Conversely, boric acid should not be always used as first line treatment, given that C. albicans does
not respond to this compound as good as C. glabrata [1–4,5]. Even if the patient we followed showed no alteration of glucose metabolism, we would suggest to always screen patients with genital C. non-albicans infections for diabetes. Given that clinical signs and symptoms in patients with C. albicans and C. glabrata infections is quite similar, gynecological and microbiological examinations should be carried out when a recurrent VVC develops (rather than treating it empirically), to exclude lower genital tract conditions (such as vulvar contact dermatitis, vulvar vestibulitis, vulvar neoplasia, lichen simplex chronicus), or confirm the VVC and subsequently test antifungal susceptibility of C. albicans and C. non-albicans isolates. Unfortunately, in vitro fungal susceptibility and clinical response to therapy do not always match. This may be due to several reasons, including in vivo biofilm formation on mucosal surfaces and local immunological factors predisposing to yeast infections. Nevertheless, species misidentification and lack of susceptibility data may lead to widespread and inappropriate use and self-use of antifungals, as well as long-term therapies and repeated treatments; this can finally result in selection of species (such as C. glabrata) exerting resistance to commonly used drugs. References [1] Savini V, Catavitello C, Manna A, et al. Two cases of vaginitis caused by itraconazole-resistant Saccharomyces cerevisiae and a review of recently published studies. Mycopathologia 2008;166(1):47–50. [2] Ribeiro MA, Dietze R, Paula CR, Da Matta DA, Colombo AL. Susceptibility profile of vaginal yeast isolates from Brazil. Mycopathologia 2000;151:5–10. [3] Khan ZU, Ahmad S, Al-Obaid I, Al-Sweih NA, Joseph L, Farhat D. Emergence of resistance to amphotericin B and triazoles in Candida glabrata vaginal isolates in a case of recurrent vaginitis. J Chemother 2008;20(4):488–91. [4] Ray D, Goswami R, Banarjee U, et al. Prevalence of Candida glabrata and its response to boric acid vaginal suppositories in comparison with oral fluconazole in patients with diabetes and vulvovaginal candidiasis. Diab care 2007;30(2):312–7. [5] Vermitsky JP, Edlind TD. Azole resistance in Candida glabrata: coordinate upregulation of multidrug transporters and evidence for a Pdr1-like transcription factor. Antimicrob Agents Chemother 2004;48:3773–81.
Vincenzo Savinia,*, Chiara Catavitelloa, Azaira Biancoa, Andrea Balbinota, Francesco D’Antoniob, Domenico D’Antonioa a Clinical Microbiology and Virology Unit, Department of Transfusion Medicine, ‘Spirito Santo’ Hospital, via Fonte Romana 8, CAP 65100, Pescara (Pe), Italy b Department of Gynecology, ‘SS. Annunziata’ Hospital, Chieti, Italy *Corresponding author. Tel.: +39 320 6265740 E-mail address: [email protected] (V. Savini) 27 April 2009 doi:10.1016/j.ejogrb.2009.06.020
Absolute shortness of the umbilical cord and hypoplasia of the ¨ lliker-Fuse complex arcuate nucleus and of the parabrachial/Ko in a case of sudden intrauterine fetal death Dear Editor, We report a case of sudden unexplained late fetal death at 41 + 4 gestational weeks, following physiological pregnancy, in which an absolute shortness of the umbilical cord was observed in association with developmental alterations of vital centers of the brainstem. Late fetal death or stillbirth is the death prior to the complete expulsion or extraction from the mother of a product of