Magill Shelley S, Shields Christine, Sears Cynthia L, Choti Michael, Merz William G
Infectious Diseases Division, Johns Hopkins University School of Medicine, 1830 E. Monument St., 4th Floor, Baltimore, MD 21205, USA.
J Clin Microbiol. 2006 Feb;44(2):529-35. doi: 10.1128/JCM.44.2.529-535.2006.
Candida spp. are common causes of bloodstream infections among hospitalized patients. Fluconazole (FLC) remains a first-line therapy for candidemia; and voriconazole (VRC), an expanded-spectrum triazole, was recently approved for the treatment of candidemia in nonneutropenic patients. In vitro studies have suggested that VRC has potent activity against Candida spp. with reduced susceptibilities to FLC. We present a case report of invasive candidiasis and candidemia due to a Candida glabrata isolate that developed resistance to all currently available triazole antifungals after a course of FLC treatment. This case prompted us to determine the frequency of cross-resistance among bloodstream Candida isolates collected during a recent 12-month period at a large, academic medical center. FLC MICs were determined for 125 of 153 isolates (81.7%). Thirty of 125 isolates (24%) were resistant or showed reduced susceptibilites to FLC (MICs >/= 16 microg/ml). When 28 of these 30 isolates were tested for their VRC susceptibilities, 9 (32%) had MICs that were >/=2 microg/ml. Five of these nine isolates were C. glabrata, two isolates were Candida tropicalis, one isolate was Candida albicans, and one isolate was Candida parapsilosis. All five Candida krusei isolates tested had VRC MICs </=0.5 microg/ml. These data have prompted the introduction of reflexive FLC susceptibility testing of first bloodstream Candida isolates at our institution. The case report and our data also suggest that VRC should be avoided as initial therapy in unstable patients with invasive candidiasis, particularly in the setting of prior azole exposure. Studies are needed to define the clinical significance of in vitro resistance to the newer antifungal agents.
念珠菌属是住院患者血流感染的常见病因。氟康唑（FLC）仍是念珠菌血症的一线治疗药物；伏立康唑（VRC）是一种广谱三唑类药物，最近被批准用于治疗非中性粒细胞减少患者的念珠菌血症。体外研究表明，VRC对念珠菌属具有强大的活性，而这些念珠菌对FLC的敏感性降低。我们报告一例侵袭性念珠菌病和念珠菌血症病例，该病例由光滑念珠菌分离株引起，在接受一个疗程的FLC治疗后，该分离株对所有目前可用的三唑类抗真菌药物均产生了耐药性。该病例促使我们确定在一家大型学术医疗中心最近12个月期间收集的血流念珠菌分离株中交叉耐药的频率。对153株分离株中的125株（81.7%）测定了FLC的最低抑菌浓度（MIC）。125株分离株中有30株（24%）对FLC耐药或敏感性降低（MIC≥16μg/ml）。当对这30株分离株中的28株进行VRC敏感性测试时，9株（32%）的MIC≥2μg/ml。这9株分离株中，5株为光滑念珠菌，2株为热带念珠菌，1株为白色念珠菌，1株为近平滑念珠菌。所有检测的5株克柔念珠菌分离株的VRC MIC≤0.5μg/ml。这些数据促使我们机构对首例血流念珠菌分离株进行FLC敏感性的回顾性检测。该病例报告和我们的数据还表明，对于患有侵袭性念珠菌病的不稳定患者，应避免将VRC作为初始治疗药物，尤其是在既往有唑类药物暴露的情况下。需要开展研究以明确体外对新型抗真菌药物耐药的临床意义。
