Chokoeva A, Kouzmanov A, Ivanova Z, Zisova L, Amalie G, Petleshkova P, Miteva-Katrandzhieva Ts, Krasteva M, Uchikova E
Akush Ginekol (Sofiia). 2016;55(4):20-29.
Background Vulvovaginal candidiasis (VVU) is considered as a special risk factor during pregnancy, with important influence on the reproductive function of the patients and on the morbidity in the newborns from mothers with VVC. Maternal VVC is a major risk factor for the development of candida-colonization of the infant, which in turn is the first step towards the development of mucocutaneous or systemic candidiasis and Candida-septicemia in the newborn. In pregnant patients, the possible applicable local and systemic medications are limited, while the therapeutic resistance in chronic recurrent forms of VVC increases, facts that require precision of the diagnosic approach to optimize the therapeutic recommendations in pregnant patients, considered as a high risk group. The aim of this study was to investigate in vitro antifungal susceptibility of Candida yeasts to current antifungal agents in pregnant patients with confirmed VVC before the act of birth. Material and Methods Vaginal secretions of 23 healthy pregnant women with proven Candida vaginitis were taken within 48 hours before birth and the presence of yeasls of Candida was confirmed by culture examination. Between 47-72 hours after birth, samples were taken for Candida colonization of the oralmucosa and feces of their newborns. Samples were plated on Sabouraud agar and cultured in an incubator for 2 to 3 days at a temperature of 25° C. Species identification of the isolated yeasts were performed by commercial API Candida test - API 20C AUX (BioMerieux, Marcy-l'Etoile, France). Part of the isolates was identified by commercial whale AUXACOLOR (BioRad, Mames la Coquette, France). Antifungal sensitivity of isolated strains was examined by applying commercial solicitation ready kit and methods of disc diffusion and E-test, as the aim of the authors was to assess their potential for use in the diagnosis, and the correlation between them. Results Candida albicans was the prevalent etiological agent in pregnant patients with VVC immediately before birth (n = 22, 91.67 +/- 0.06%). Positive Candida colonization was detected in 14 (58.33%) of their newborns (n = 24), as no statistically significant difference was established, depending on the mode of delivery. The investigated antifungal susceptibility with test Fungifast (ELITech Microbiology Reagents), found 100% sensitivity of Candida albicans to Amphotericin B, Flucytosin and Voriconazole. Intermediate susceptibility to Itraconazole was found in 6 of 23 (26%) maternal isolates, and 5 of 23 (22%) isolates were moderately sensitive to Fluconazole. Candida krusei showed complete resistance to Fluconazole and Itraconazole. Within the group of antifungals for topical application (Econazole, Ketoconazole, Miconazole, Nystatin), the results established that 100% of the studied fungi were sensitive to Nystatin, while within the groups of azoles for vaginal and topical use - C.krusei was 100% resistant, as the sensitivity of C. albicans varied between 60-80%. Conclusion Our recommendation, based on the esablished results is that in pregnant with uncomplicated VVC as a first-line therapy should be considered the group of vaginal azoles and Nystatin, while the systemic therapy should be considered carefully and only after the firSt trimester. In cases of oral and intestinal candidiasis in neonatology, we recommend a therapy with minimal absorbable antifungals as Nystatin and miconazole (amphotericin B is available in our country), while systemic antifungal should be initiated only as a second choice. The exact etiological diagnosis is especially important because in our country there is a tendency for increased incidence of non-albicans fungus resistant to therapy, and that changes the therapeutic behavior.
背景 外阴阴道念珠菌病(VVU)被认为是孕期的一个特殊风险因素,对患者的生殖功能以及患VVC母亲所生新生儿的发病率有重要影响。母亲的VVC是婴儿念珠菌定植发展的主要风险因素,而这反过来又是新生儿发生黏膜皮肤或全身性念珠菌病及念珠菌败血症的第一步。在孕妇中,可能适用的局部和全身用药有限,而慢性复发性VVC的治疗耐药性增加,这些事实要求在诊断方法上做到精准,以优化对作为高风险群体的孕妇的治疗建议。本研究的目的是在分娩前对确诊为VVC的孕妇中念珠菌酵母对当前抗真菌药物的体外抗真菌敏感性进行调查。
材料与方法 在23例经证实患有念珠菌性阴道炎的健康孕妇分娩前48小时内采集阴道分泌物,并通过培养检查确认念珠菌酵母的存在。在出生后47 - 72小时之间,采集其新生儿口腔黏膜和粪便的念珠菌定植样本。将样本接种在沙保弱琼脂上,并在25°C的培养箱中培养2至3天。通过商业API念珠菌检测 - API 20C AUX(法国生物梅里埃公司,马西 - 埃图瓦勒)对分离出的酵母进行菌种鉴定。部分分离株通过商业鲸鱼AUXACOLOR(法国伯乐公司,马梅斯拉科凯特)进行鉴定。应用商业药敏试剂盒以及纸片扩散法和E-test法检测分离菌株的抗真菌敏感性,因为作者的目的是评估它们在诊断中的应用潜力以及它们之间的相关性。
结果 白色念珠菌是分娩前患有VVC的孕妇中最常见的病原体(n = 22,91.67±0.06%)。在其24例新生儿中有14例(58.33%)检测到念珠菌定植呈阳性,根据分娩方式未发现统计学上的显著差异。使用Fungifast(ELITech微生物试剂公司)检测抗真菌敏感性发现,白色念珠菌对两性霉素B、氟胞嘧啶和伏立康唑的敏感性为100%。在23例母体分离株中有6例(26%)对伊曲康唑呈中度敏感,23例分离株中有5例(22%)对氟康唑呈中度敏感。克柔念珠菌对氟康唑和伊曲康唑表现出完全耐药。在局部应用的抗真菌药物组(益康唑、酮康唑、咪康唑、制霉菌素)中,结果表明所研究的真菌对制霉菌素的敏感性为100%,而在阴道和局部使用的唑类药物组中 - 克柔念珠菌的耐药性为100%,白色念珠菌的敏感性在60 - 80%之间变化。
结论 根据已确立的结果,我们的建议是,对于患有单纯性VVC的孕妇,一线治疗应考虑阴道唑类药物组和制霉菌素,而全身治疗应谨慎考虑,且仅在孕早期之后。在新生儿科出现口腔和肠道念珠菌病的情况下,我们建议使用吸收性最小的抗真菌药物如制霉菌素和咪康唑进行治疗(我国有两性霉素B),而全身抗真菌治疗仅应作为第二选择。准确的病因诊断尤为重要,因为在我国,对治疗耐药的非白色念珠菌的发病率有上升趋势,这会改变治疗方式。