Cross-resistance between voriconazole and fluconazole for non-albicans Candida infection: a case-case-control study
Cross-resistance between voriconazole and fluconazole for non-albicans Candida infection: a case-case-control study
复制标题
伏立康唑和氟康唑治疗非白色念珠菌感染的交叉耐药性：病例对照研究
DOI：
10.1007/s10096-017-3034-4
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发表时间：
2017-11-01
影响因子：
4.5
通讯作者：
Dong, Y.
中科院分区：
文献类型：
--
作者：
Wang, Y.;Yang, Q.;Dong, Y.
伏立康唑和氟康唑对非白念珠菌（NAC）的交叉耐药（CR）并不少见，但对与这种耐药表型相关的风险因素和临床后果知之甚少。2012年11月至2016年4月在中国的一所大学附属医院进行了一项病例-病例-对照研究。两个病例组分别包括单耐药（MR）NAC感染（氟康唑或伏立康唑耐药）和CR NAC感染（氟康唑和伏立康唑耐药）的患者。无耐药（NR）NAC感染的患者作为对照组。根据人口统计学和临床风险因素调整模型，并评估与暴露于特定抗生素或非抗生素相关的耐药风险。在259次发作中，分别有33次（12.7%）和27次（10.4%）被确定为MR和CR NAC感染。唑类药物的广泛使用与MR和CR NAC感染的出现密切相关（校正比值比[95%置信区间]分别为2.69 [1.10 - 6.58]和2.53 [1.02 - 6.28]）。以12天为断点的风险时间（1.02 [1.00 - 1.03]）也是CR NAC感染的独立风险因素。CR NAC感染中与最低抑菌浓度（≥ 128 μ g/mL）较高的氟康唑相关的菌种数量高于MR NAC感染。不同的耐药表型（CR vs. MR vs. NR）与全因死亡率相关。这些发现表明CR NAC感染的倾向令人担忧，并强调需要严格的抗真菌药物管理。
Cross-resistance (CR) between voriconazole and fluconazole for non-albicans Candida (NAC) species is not uncommon, but little is known about the risk factors and clinical consequences associated with this resistance phenotype. A case-case-control study was performed at a university-affiliated hospital in China between November 2012 and April 2016. The two case groups respectively comprised patients with a mono-resistance (MR) NAC infection (fluconazole or voriconazole resistance) and patients with a CR NAC infection (fluconazole and voriconazole resistance). Patients with a no-resistance (NR) NAC infection were included as the control group. Models were adjusted for demographic and clinical risk factors, and the risk of resistance associated with exposure to specific antibiotics or non-antibiotics were assessed. Of 259 episodes, 33 (12.7%) and 27 (10.4%) were identified as MR and CR NAC infections, respectively. The broad use of azoles was strongly associated with the emergence of MR and CR NAC infections (adjusted odds ratio [95% confidence interval] = 2.69 [1.10–6.58] and 2.53 [1.02–6.28], respectively). The time at risk (1.02 [1.00–1.03]) with 12 days as a breakpoint was also an independent risk factor for CR NAC infection. The number of species associated with a high minimum inhibitory concentration (≥128 μg/mL) of fluconazole was higher for CR NAC infections than for MR NAC infections. Different resistance phenotypes (CR vs. MR vs. NR) were associated with all-cause mortality rates. These findings indicate a worrisome propensity of CR NAC infections and emphasize the need for strict antifungal stewardship.