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[新生儿念珠菌感染及相关念珠菌属的抗真菌药敏性]

[Neonatal Candida infections and the antifungal susceptibilities of the related Candida species].

作者信息

Altuncu Emel, Bilgen Hülya, Cerikçioğlu Nilgün, Ilki Arzu, Ulger Nurver, Bakır Mustafa, Akman Ipek, Ozek Eren

机构信息

Marmara Üniversitesi Tıp Fakültesi, Çocuk Sağlığı ve Hastalıkları Anabilim Dalı, Yenidoğan Bilim Dalı, İstanbul, Türkiye.

出版信息

Mikrobiyol Bul. 2010 Oct;44(4):593-603.

PMID:21063972
Abstract

Among nosocomial infections in the newborns, the incidence of fungal infections has been rising over the last decades. Fluconazole has been a new option for treatment however, expanded use of the drug brought up the development of resistance. In this study, species of the Candida isolates from neonates with candida infections, their antifungal susceptibilities and the effectiveness of the therapy were evaluated. All the species of Candida isolates from blood, urine and sterile body fluids of 54 neonates and their antifungal susceptibilities were evaluated retrospectively over the 13-year period. Demographic characteristics, risk factors, infection foci, Candida species causing infection and their in vitro susceptibilities for fluconazole (FCZ) and amphotericin B (AMB) and treatment responses were analyzed. The antifungal susceptibility testing of isolates was performed by microdilution technique. The median birth weight and gestational age of the study groups were 1735 (660-3990) g and 33 (24-40) weeks, respectively. Among the patients, 19 (35%) were term, while 35 (65%) were preterm [< 32 weeks n = 20 (37%), < 28 weeks n = 7 (13%)]. The percentage of low birth weight infants was 65% (42% was < 1500 g, 13% was < 1000 g). Candida spp. were isolated mostly from blood samples (63%), followed by urine (46%), cerebrospinal fluid (CSF; 5%), peritoneal fluid (3%) and endotracheal aspirate (2%). Multifocal growth was determined in 10 (18%) cases. The isolated species were C.albicans (n =36) as being the most common isolate followed by C.parapsilosis (n = 12), C.tropicalis (n = 1), C.kefyr (n = 1), C.lusitaniae (n = 1), C.pelluculosa (n = 1) and Candida spp. (n = 2). Prior antibiotic use, long term hospitalization, total parenteral nutrition and use of lipid solutions, prematurity and catheter use were determined as the most frequently associated factors causing candidal infections. A congenital abnormality, mainly myeloschisis and hydrocephaly, was detected in 18 (33%) of the cases. Overall FCZ resistance rate was 5.5% and the rate of resistance according to the species was 2.8% for C.albicans and 11% for non-albicans isolates. No resistance was observed to AMB. Initial treatment was FCZ for 78% and AMB for 22% of the newborns. The treatment was switched to AMB in 15 (28%) cases because of no clinical or laboratory response to FCZ although only three of these babies showed resistance to FCZ (MIC ≥ 64 mcg/ml). Among the cases with no clinical/microbiological response, C.albicans was the most frequently (66%) isolated species followed by non-albicans species (33%). All of the isolates in the study group were susceptible to AMB and the rate of FCZ resistance was 5.5%. However, it was noted that the clinical treatment failure was higher than the resistance rate when FCZ was considered. Although antifungal susceptibility tests are helpful for guiding the therapy, in vivo and in vitro differences should be taken into account in case of treatment failure encountered with the use of in vitro effective agents.

摘要

在新生儿医院感染中,真菌感染的发生率在过去几十年里一直在上升。氟康唑一直是一种新的治疗选择,然而,该药物的广泛使用导致了耐药性的产生。在本研究中,对念珠菌感染新生儿分离出的念珠菌种类、它们的抗真菌药敏性以及治疗效果进行了评估。回顾性评估了13年间从54例新生儿的血液、尿液和无菌体液中分离出的所有念珠菌种类及其抗真菌药敏性。分析了人口统计学特征、危险因素、感染灶、引起感染的念珠菌种类及其对氟康唑(FCZ)和两性霉素B(AMB)的体外药敏性以及治疗反应。采用微量稀释技术对分离株进行抗真菌药敏试验。研究组的中位出生体重和胎龄分别为1735(660 - 3990)g和33(24 - 40)周。在这些患者中,19例(35%)为足月儿,35例(65%)为早产儿[<32周n = 20例(37%),<28周n = 7例(13%)]。低出生体重儿的比例为65%(<1500g的占42%,<1000g的占13%)。念珠菌属大多从血液样本中分离出来(63%),其次是尿液(46%)、脑脊液(CSF;5%)、腹腔液(3%)和气管内吸出物(2%)。10例(18%)病例中发现多灶性生长。分离出的菌种以白色念珠菌(n = 36)最为常见,其次是近平滑念珠菌(n = 12)、热带念珠菌(n = 1)、克柔念珠菌(n = 1)、葡萄牙念珠菌(n = 1)、光滑念珠菌(n = 1)和念珠菌属(n = 2)。先前使用抗生素、长期住院、全胃肠外营养和脂质溶液的使用、早产和使用导管被确定为引起念珠菌感染最常见的相关因素。18例(33%)病例中检测到先天性异常,主要是脊柱裂和脑积水。总体FCZ耐药率为5.5%,按菌种计算,白色念珠菌的耐药率为2.8%,非白色念珠菌分离株的耐药率为11%。未观察到对AMB耐药的情况。78%的新生儿初始治疗使用FCZ,22%使用AMB。15例(28%)病例因对FCZ无临床或实验室反应而改用AMB,尽管这些婴儿中只有3例对FCZ耐药(MIC≥64 mcg/ml)。在无临床/微生物学反应的病例中,白色念珠菌是最常分离出的菌种(66%),其次是非白色念珠菌(33%)。研究组所有分离株对AMB敏感,FCZ耐药率为5.5%。然而,值得注意的是,当考虑FCZ时,临床治疗失败率高于耐药率。尽管抗真菌药敏试验有助于指导治疗,但在使用体外有效的药物遇到治疗失败时,应考虑体内和体外的差异。

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