Clinical Impact of Polymerase Chain Reaction–Based Aspergillus and Azole Resistance Detection in Invasive Aspergillosis: A Prospective Multicenter Study
Clinical infectious diseases, 2023
要点
・オランダ・ベルギー12施設の血液悪性腫瘍＋新規肺浸潤影→BALF検体を AsperGenius PCR キットを用いて検査
・293名中116名でAsperugillus DNA(89名A.fumigatus検出) 耐性は約14%
・培養は23名でのみ検出, GM1.0以上でも検出率は23%
要約：
・試験施設：オランダ・ベルギー：12施設
・対象：血液悪性腫瘍＋CTで新規肺浸潤影（BALF48時間以内に施行目的）
・介入：BALFでAsperGenius PCR
（アスペルギルス同定＋アゾール耐性検出：cyp51A gene変異）
TR34/L98H, TR46/T289A/Y121F
結果：
・2017-2021: 323名が条件を満たし、293名でAsperugillus PCR
・116名でAsperugillus DNA （89名でA. fumigatus）
Galactomannan抗原（<0.5, 0.5-0.99, ≧1.0） で3つに分類
・89名中58名（65%）で変異解析が可能→8名で変異を検出
アスペルギルス培養は323名のBALF中23名で検出, GM1.0以上でも検出率は23%
：一部で薬剤感受性が実施でき、薬剤耐性遺伝子と耐性は一致
・GM値毎でのPCR検出率は<0.5で26％、0.5-0.99で52%, >1.0で74%
Background
Invasive aspergillosis (IA) by a triazole-resistant Aspergillus fumigatus is associated with high mortality. Real-time resistance detection will result in earlier initiation of appropriate therapy.
Methods
In a prospective study, we evaluated the clinical value of the AsperGenius polymerase chain reaction (PCR) assay in hematology patients from 12 centers. This PCR assay detects the most frequent cyp51A mutations in A. fumigatus conferring azole resistance. Patients were included when a computed tomography scan showed a pulmonary infiltrate and bronchoalveolar fluid (BALf) sampling was performed. The primary end point was antifungal treatment failure in patients with azole-resistant IA.
Results
Of 323 patients enrolled, complete mycological and radiological information was available for 276 (94%), and probable IA was diagnosed in 99/276 (36%). Sufficient BALf for PCR testing was available for 293/323 (91%). Aspergillus DNA was detected in 116/293 (40%) and A. fumigatus DNA in 89/293 (30%). The resistance PCR was conclusive in 58/89 (65%) and resistance detected in 8/58 (14%). Two had a mixed azole-susceptible/azole-resistant infection. In the 6 remaining patients, treatment failure was observed in 1. Galactomannan positivity was associated with mortality (P = .004) while an isolated positive Aspergillus PCR was not (P = .83).
Conclusions
Real-time PCR-based resistance testing may help to limit the clinical impact of triazole resistance. In contrast, the clinical impact of an isolated positive Aspergillus PCR on BALf seems limited. The interpretation of the EORTC/MSGERC PCR criterion for BALf may need further specification (eg, minimum cycle threshold value and/or PCR positive on >1 BALf sample).
