Role of prospective screening of blood for invasive aspergillosis by polymerase chain reaction in febrile neutropenic recipients of haematopoietic stem cell transplants and patients with acute leukaemia

Abstract

Summary Guidelines for the use of polymerase chain reaction (PCR)‐based assays to aid the diagnosis of invasive aspergillosis (IA) in high‐risk haematology patients have not been formulated. We prospectively evaluated a nested PCR assay to detect Aspergillus in blood during 95 febrile neutropenic episodes, in patients with haematological malignancy and haematopoietic stem cell transplant (HSCT) recipients. PCR results were correlated with the diagnostic classification of the 2002 European Organisation for Research and Treatment of Cancer/Mycosis Study Group. When two‐positive results were used to define an episode as ‘PCR positive’, the sensitivity, specificity, positive‐predictive value and negative predictive value for ‘proven’/‘probable’ IA (n = 13) were 100%, 75·4%, 46·4% and 100%, respectively. Consecutive positive results occurred in 61·5% of these 13 episodes. Overall, PCR positivity preceded standard diagnosis by a mean of 14 d and the median time between positive results was shorter than that in other categories of IA. All 13 episodes occurred in the setting of allogeneic HSCT recipients and acute leukaemia. If ‘eligibility’ for antifungal therapy were based on two‐positive‐PCR tests, use of empiric treatment could have been reduced by up to 37%. The nested PCR assay is a practical screening test for excluding IA. Patients with consecutive positive results or intermittent‐positive results (within 14 d) warrant immediate investigations for IA and the initiation of antifungal therapy.

Randomized PCR-based therapy and risk factors for invasive fungal infection following reduced-intensity conditioning and hematopoietic SCT

“…15,17,34 No conclusions regarding multiple [15][16][17]34,35 In our study, we did not find that PCR tests for Aspergillus were useful in patients with proven or probable IA. Fungal PCR tests were performed within 2 weeks of diagnosis in six of nine patients with proven or probable IA, and only one patient had a positive PCR test.…”

“…Although the results have been variable, the authors of some of these reports have concluded that PCR contributes to establishment of the diagnosis of IFI. [15][16][17] It has also been reported that a positive PCR test precedes the clinical diagnosis of invasive aspergillosis (IA), by several days up to several weeks. 15,16 These findings raise the question of whether PCR-guided early antifungal treatment could reduce the incidence and mortality of IFI after HSCT, in an analogous way to the successful development of pre-emptive treatment of CMV.…”

“…[15][16][17] It has also been reported that a positive PCR test precedes the clinical diagnosis of invasive aspergillosis (IA), by several days up to several weeks. 15,16 These findings raise the question of whether PCR-guided early antifungal treatment could reduce the incidence and mortality of IFI after HSCT, in an analogous way to the successful development of pre-emptive treatment of CMV. 20 To answer this question, we performed a prospective study in which patients with a positive fungal PCR result within 100 days of RIC HSCT were randomized to receive either treatment with liposomal amphotericin B or no treatment.…”

“…In recent years, noninvasive diagnostic techniques such as PCR-based assays capable of detecting DNA from Aspergillus and Candida species have been developed. [14][15][16][17][18][19] Several PCR protocols for detection of fungal DNA in blood have been used, with a wide range of sensitivity and specificity. Although the results have been variable, the authors of some of these reports have concluded that PCR contributes to establishment of the diagnosis of IFI.…”

Pulmonary aspergillosis: a clinical review

“…The sensitivity and specificity of PCR of BAL fluid samples are estimated to be 67-100% and 55-95%, respectively [111], while for serum samples the sensitivity and specificity have been reported as 100% and 65-92%, respectively [111][112][113][114]. However, PCR is often associated with false-positive results, because it does not discriminate between colonisation and infection.…”