Prospective screening by a panfungal polymerase chain reaction assay in patients at risk for fungal infections: implications for the management of febrile neutropenia

Abstract

Summary. Invasive fungal infections are a major cause of mortality in neutropenic cancer patients. To determine whether a polymerase chain reaction (PCR)-based assay enabled the identification of patients at risk for invasive fungal infections, a prospective monitoring once per week was performed during 92 neutropenic episodes in patients receiving chemotherapy for acute leukaemia or high-dose therapy followed by allogeneic or autologous stem cell transplantation, with the investigators blinded to clinical and microbiological data. PCR positivity was documented in 34 out of 92 risk episodes. All patients developing proven invasive fungal infection were found PCR positive, and PCR was found to be the earliest indicator of invasive fungal infection preceding clinical evidence by a mean of 5´75 d (range 0±14 d). In febrile neutropenic patients without a prior history of invasive fungal infection, a sensitivity of 100% and a specificity of 73% of the PCR assay for the development of proven or probable invasive fungal infection was documented. In conclusion, panfungal PCR performed prospectively once a week enabled the identification of patients at high risk for invasive fungal infections.

Preemptive Treatment of Fungal Infection Based on Plasma (1 → 3)β-D-Glucan Levels after Liver Transplantation

“…Polymerase chain reaction assays [17][18][19][20] or serum antigen assays [21][22][23][24][25][26] are useful for detecting specific fungi in blood or bronchoalveolar lavage are useful, but they are limited in specificity and are costly. Culture of specimens from the lesion might have low sensitivity to the presence or absence of fungal infection and be time consuming [27].…”

Challenges and progress in setting a standard for PCR for invasive aspergillosis

“…Clearly, there is a high LR+ only for the study of Raad et al [18]. The studies of Halliday et al [12•], Hebart et al [13,14], and Scotter et al [19] all yielded a high LR-but very low LR+. Hence, the studies all performed differently, with some leaning toward a high negative-predictive value, one toward a high positive-predictive value, and the remainder appearing indifferent.…”

“…In preparing a systematic review with Carlo Mengoli of the Department of Histology, Microbiology, and Medical Biotechnology, University of Padua, Padua, Italy and Mario Cruciani from the Centre of Preventive Medicine, HIV Outpatient Clinic, Verona, Italy based on the review of Boudewijns et al [5], we identifi ed 16 prospective cohort studies of consecutive patients at high risk for invasive aspergillosis akin to phase 2 drug studies [3,6-8,9•,10,11,12•, [13][14][15][16][17][18][19][20]. All compared the results of PCR with the diagnosis made following the original defi nitions for invasive fungal disease proposed by the EORTC/MSG or, for studies reported before the publication of these criteria in 2002, comparable criteria as a reference standard [1].…”

Fungal endocarditis

“…The advantages of PCR include relative rapidity, ability to amplify a small amount of fungal material without the need for viable fungi, relative simplicity, and the general availability of the necessary equipment. It has been shown that positive PCR preceded the clinical evidence of invasive fungal infections by a mean of 5.7 days in hematology patients, supporting the high sensitivity of this method [29]. In several prospective trials in hematology patients, fungal DNA detection by PCR was shown to be highly sensitive but with modest positive predictive value because of many false-positive results [27•].…”