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HIV感染患者念珠菌分离株对抗真菌药物的敏感性及体内外相关性的横断面研究。

Cross-sectional study of the susceptibility of Candida isolates to antifungal drugs and in vitro-in vivo correlation in HIV-infected patients.

作者信息

Chavanet P, Lopez J, Grappin M, Bonnin A, Duong M, Waldner A, Buisson M, Camerlynck P, Portier H

机构信息

Department of Tropical and Infectious Diseases, Bocage Hospital, Dijon, France.

出版信息

AIDS. 1994 Jul;8(7):945-50. doi: 10.1097/00002030-199407000-00011.

DOI:10.1097/00002030-199407000-00011
PMID:7946104
Abstract

OBJECTIVES

To investigate (1) the frequency of clinical resistance to oral polyenes or azole treatment for oral candidiasis, (2) the frequency of resistant in vitro Candida strains, (3) the relationship between the susceptibilities of in vitro Candida species and in vivo status in HIV patients.

DESIGN

Prospective cross-sectional study.

SETTING

Tertiary care clinic at Bocage Hospital, Dijon, France.

PATIENTS

HIV-infected patients with and without oral candidiasis.

INTERVENTIONS

Clinical examination, oral swab for mycologic investigations.

MAIN OUTCOME MEASURES

Clinical diagnosis of oral candidiasis, identification of the antifungal treatment given within the previous month, identification of Candida species, antimycogramm and determination of the minimal inhibitory concentration (MIC) for fluconazole, and measurement of T-helper cell count.

RESULTS

Within a 2-month period, 154 HIV-infected patients were studied: 46 heterosexuals, 51 intravenous drug users (IVDU), 52 homosexuals and five blood transfusion recipients. The percentages of patients with oral candidiasis were: 41, 80, 44 and 20%, respectively (P < 0.05); the mean T-helper cell counts were 200, 135, 210 and 238 x 10(6)/l cells, respectively (P < 0.05). Twenty-two patients (14.3%) had received recent azole treatment and 29 (18.8%) recent oral polyene treatment. Among the 84 patients with and the 70 patients without oral candidiasis, 78 and 28 Candida strains were isolated, respectively. Although Candida albicans represented the majority of Candida species (88 strains, 83%), the non-albicans strains were isolated more frequently in patients who had received recent antifungal treatment. No strains were resistant to ketoconazole, miconazole or econazole; however, six (5.6%), 16 (15%) and 10 (9.5%) were intermediately susceptible to the three drugs, respectively. Twelve (13.6%) of the 88 C. albicans, five of the six C. (Torulopsis) glabrata, one of the five C. tropicalis and all three C. krusei strains were resistant to fluconazole. These resistant strains were separated as follows: 41.1% of C. albicans strains resistant to fluconazole were isolated from patients who had received recent azole therapy, 17.6% from patients who received recent oral polyene, and 3.7% from patients who had not received any recent antifungal treatment (P = 0.004). The mean MIC of these three categories of isolates were 3.6, 1.6 and 0.6 mg/l, respectively (P = 0.06).

CONCLUSIONS

Oral candidiasis and fluconazole-resistant Candida isolates are more frequently found in IVDU. Treatments using azoles select non-albicans strains and are associated with decreased susceptibilities of C. albicans strains to fluconazole in particular. These findings show that prolonged azole treatment in severely immunocompromised patients should be avoided.

摘要

目的

调查(1)口腔念珠菌病患者对口服多烯类或唑类治疗产生临床耐药性的频率;(2)念珠菌体外菌株的耐药频率;(3)HIV患者体内念珠菌种类的药敏性与体内状况之间的关系。

设计

前瞻性横断面研究。

地点

法国第戎博卡日医院的三级护理诊所。

患者

患有和未患有口腔念珠菌病的HIV感染患者。

干预措施

临床检查、口腔拭子用于真菌学检查。

主要观察指标

口腔念珠菌病的临床诊断、前一个月内接受的抗真菌治疗的鉴定、念珠菌种类的鉴定、抗真菌药敏试验以及氟康唑最低抑菌浓度(MIC)的测定,以及辅助性T细胞计数的测量。

结果

在2个月的时间内,对154例HIV感染患者进行了研究:46例异性恋者、51例静脉吸毒者(IVDU)、52例同性恋者和5例输血接受者。患有口腔念珠菌病的患者百分比分别为:41%、80%、44%和20%(P<0.05);辅助性T细胞平均计数分别为200、135、210和238×10⁶/l细胞(P<0.05)。22例患者(14.3%)近期接受了唑类治疗,29例患者(18.8%)近期接受了口服多烯类治疗。在84例患有口腔念珠菌病的患者和70例未患口腔念珠菌病的患者中,分别分离出78株和28株念珠菌菌株。虽然白色念珠菌是念珠菌种类中的大多数(88株,83%),但在近期接受抗真菌治疗的患者中,非白色念珠菌菌株的分离更为频繁。没有菌株对酮康唑、咪康唑或益康唑耐药;然而,分别有6株(5.6%)、16株(15%)和10株(9.5%)对这三种药物中度敏感。88株白色念珠菌中的12株(13.6%)、6株光滑念珠菌(Torulopsis)中的5株、5株热带念珠菌中的1株以及所有3株克柔念珠菌菌株对氟康唑耐药。这些耐药菌株的分布如下:对氟康唑耐药的白色念珠菌菌株中,41.1%分离自近期接受唑类治疗的患者,17.6%分离自近期接受口服多烯类治疗的患者,3.7%分离自近期未接受任何抗真菌治疗的患者(P=0.004)。这三类分离株的平均MIC分别为3.6、1.6和0.6mg/l(P=0.06)。

结论

IVDU中口腔念珠菌病和氟康唑耐药念珠菌分离株更为常见。使用唑类进行治疗会选择非白色念珠菌菌株,尤其会导致白色念珠菌菌株对氟康唑的药敏性降低。这些发现表明,应避免在严重免疫功能低下的患者中长时间使用唑类治疗。

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