P474 The value of PCR-based azole resistance detection in invasive aspergillosis: A prospective multicenter study

Abstract

Abstract Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM Objectives Prompt detection of azole-resistant Aspergillus fumigatus will result in the timely start of active treatment and may improve the survival of invasive aspergillosis (IA). The use of a multiplex polymerase chain reaction (PCR) targeting Aspergillus species and fumigatus DNA as well as the two most prevalent azole resistance- associated mutations (RAMs) in the cyp51A gen (TR34/L98H and TR46/Y121F/T289A) could shorten the time to detect azole-resistant IA. Methods In a prospective study in 12 Dutch and Belgian centers, we evaluated the clinical value of the multiplex AsperGenius®PCR in hematology patients with a pulmonary infiltrate undergoing bronchoalveolar lavage (BALf) sampling. The primary endpoint was antifungal treatment failure in the 6 weeks after antifungal treatment initiation in the patients in which azole-resistant IA was detected. Treatment failure was defined as death or a switch to an antifungal agent from another class after at least 5 days of first-line therapy. Patients with a mixed azole-susceptible/resistant infection were excluded from this analysis to ascertain that the infection was indeed caused by the resistant strain. Results Of 323 patients enrolled, sufficient BALf for PCR testing remained in 299. Probable fungal disease was diagnosed in 95 (34%), Aspergillus cultured in 24 (8%), Aspergillus DNA detected in 118 (39%), and A. fumigatus DNA in 88 (29%) patients. The resistance PCR was conclusive in 54/88 (61%) and RAMs were detected in 8 (15%), Table 1. All 8 had probable IA but 2 had a mixed infection and were excluded. In the 6 remaining patients, treatment failure was observed in one. Compared with the GM negative patients and despite antifungal therapy, a positive GM test was associated with a 13% higher 6-week overall mortality (P = .01), Table 2. Surprisingly, the 6-week mortality in the 65 patients who had a positive Aspergillus PCR but a negative GM and culture was not increased compared to those with a negative PCR (PCR + 14% vs. PCR- 16% mortality, P = .68). Conclusions In patients with an underlying hematological disease and a pulmonary infiltrate, the detection of Aspergillus DNA by PCR on BALf was not associated with increased mortality. The exact place of the Aspergillus PCR in the EORTC-MSGERC invasive fungal infection criteria is therefore uncertain. In 15% of the patients in whom A. fumigatus DNA was present, azole RAMs were detected by PCR. In only 1/6 probable cases of IA with RAMs detected, antifungal treatment failure was observed. Basing the choice of antifungal therapy on the result of a cyp51a resistance PCR may help to reduce the impact of azole resistance on mortality.