Abstract：
BACKGROUND: Azole resistance complicates treatment of patients with invasive aspergillosis with an increased mortality. Azole resistance in Aspergillus fumigatus is a growing problem and associated with human and environmental azole use. Denmark has a considerable and highly efficient agricultural sector. Following reports on environmental azole resistance in A. fumigatus from Danish patients, the ministry of health requested a prospective national surveillance of azole-resistant A. fumigatus and particularly that of environmental origin.
OBJECTIVE: To present the data from the first 2 years of the surveillance programme.
METHODS: Unique isolates regarded as clinically relevant and any A. fumigatus isolated on a preferred weekday (background samples) were included. EUCAST susceptibility testing was performed and azole-resistant isolates underwent cyp51A gene sequencing.
RESULTS: The azole resistance prevalence was 6.1% (66/1083) at patient level. The TR34 /L98H prevalence was 3.6% (39/1083) and included the variants TR34 /L98H, TR34 3 /L98H and TR34 /L98H/S297T/F495I. Resistance caused by other Cyp51A variants accounted for 1.3% (14/1083) and included G54R, P216S, F219L, G54W, M220I, M220K, M220R, G432S, G448S and Y121F alterations. Non-Cyp51A-mediated resistance accounted for 1.2% (13/1083). Proportionally, TR34 /L98H, other Cyp51A variants and non-Cyp51A-mediated resistance accounted for 59.1% (39/66), 21.2% (14/66) and 19.7% (13/66), respectively, of all resistance. Azole resistance was detected in all five regions in Denmark, and TR34 /L98H specifically, in four of five regions during the surveillance period.
CONCLUSIONS: The azole resistance prevalence does not lead to a change in the initial treatment of aspergillosis at this point, but causes concern and leads to therapeutic challenges in the affected patients.
OBJECTIVE: To present the data from the first 2 years of the surveillance programme.
METHODS: Unique isolates regarded as clinically relevant and any A. fumigatus isolated on a preferred weekday (background samples) were included. EUCAST susceptibility testing was performed and azole-resistant isolates underwent cyp51A gene sequencing.
RESULTS: The azole resistance prevalence was 6.1% (66/1083) at patient level. The TR34 /L98H prevalence was 3.6% (39/1083) and included the variants TR34 /L98H, TR34 3 /L98H and TR34 /L98H/S297T/F495I. Resistance caused by other Cyp51A variants accounted for 1.3% (14/1083) and included G54R, P216S, F219L, G54W, M220I, M220K, M220R, G432S, G448S and Y121F alterations. Non-Cyp51A-mediated resistance accounted for 1.2% (13/1083). Proportionally, TR34 /L98H, other Cyp51A variants and non-Cyp51A-mediated resistance accounted for 59.1% (39/66), 21.2% (14/66) and 19.7% (13/66), respectively, of all resistance. Azole resistance was detected in all five regions in Denmark, and TR34 /L98H specifically, in four of five regions during the surveillance period.
CONCLUSIONS: The azole resistance prevalence does not lead to a change in the initial treatment of aspergillosis at this point, but causes concern and leads to therapeutic challenges in the affected patients.
摘要：
背景：唑耐药使侵袭性曲霉病患者的治疗复杂化，死亡率增加。烟曲霉的唑抗性是一个日益严重的问题，与人类和环境唑的使用有关。丹麦拥有相当大的高效农业部门。根据丹麦患者烟曲霉对环境唑的耐药性报告，卫生部要求对耐唑的烟曲霉，特别是环境来源的，进行前瞻性的国家监测。
目的：提供监测项目前2年的数据。
方法:包括被认为是临床相关的独特分离株和在优选工作日分离的任何烟曲霉(背景样品)。进行了EUCAST药敏试验，并对耐药唑的分离株进行了cyp51A基因测序。
结果：患者水平的唑类耐药率为6.1%（66/1083）。TR34/L98H患病率为3.6%（39/1083），包括TR34/L98H变体，TR343/L98H和TR34/L98H/S297T/F495I。由其他Cyp51A变体引起的抗性占1.3％（14/1083），包括G54R，P216S,F219L,G54W,M220I,M220K,M220R,G432S,G448S和Y121F改变。非Cyp51A介导的耐药性占1.2%(13/1083)。按比例,TR34/L98H,其他Cyp51A变体和非Cyp51A介导的抗性占59.1%（39/66），21.2%(14/66)和19.7%(13/66)，分别,所有的抵抗。在丹麦的所有五个地区都检测到唑抗性，特别是TR34/L98H，在监测期间，五个地区中的四个地区。
结论：在这一点上，唑类耐药率并没有导致曲霉菌病初始治疗的改变，但在受影响的患者中引起关注并导致治疗挑战。
目的：提供监测项目前2年的数据。
方法:包括被认为是临床相关的独特分离株和在优选工作日分离的任何烟曲霉(背景样品)。进行了EUCAST药敏试验，并对耐药唑的分离株进行了cyp51A基因测序。
结果：患者水平的唑类耐药率为6.1%（66/1083）。TR34/L98H患病率为3.6%（39/1083），包括TR34/L98H变体，TR343/L98H和TR34/L98H/S297T/F495I。由其他Cyp51A变体引起的抗性占1.3％（14/1083），包括G54R，P216S,F219L,G54W,M220I,M220K,M220R,G432S,G448S和Y121F改变。非Cyp51A介导的耐药性占1.2%(13/1083)。按比例,TR34/L98H,其他Cyp51A变体和非Cyp51A介导的抗性占59.1%（39/66），21.2%(14/66)和19.7%(13/66)，分别,所有的抵抗。在丹麦的所有五个地区都检测到唑抗性，特别是TR34/L98H，在监测期间，五个地区中的四个地区。
结论：在这一点上，唑类耐药率并没有导致曲霉菌病初始治疗的改变，但在受影响的患者中引起关注并导致治疗挑战。
