Aspergillus PCR in serum for the diagnosis, follow-up and prognosis of invasive aspergillosis in neutropenic and non-neutropenic patients

We evaluated the usefulness of a serum Aspergillus PCR assay for the diagnosis and prognosis of invasive aspergillosis in a study involving 941 patients for a total of 5,146 serum samples. Fifty-one patients had proven/probable aspergillosis. We compared galactomannan, PCR, and mycological analysis of pulmonary samples in both neutropenic and non-neutropenic patients. PCR performed in serum yielded 66.7% sensitivity, 98.7% specificity, 75.6% positive predictive value and 98.0% negative predictive value while the galactomannan index yielded 78.4% sensitivity, 87.5% specificity, 27% positive predictive value and 98.6% negative predictive value. The inclusion of PCR in the EORTC/MSG mycological criteria permitted the reclassification of nine other cases from possible to probable aspergillosis and increased sensitivity to 71.7%. Combining the galactomannan index with serum PCR increased the detection rate of invasive aspergillosis with 88.2% sensitivity. PCR was systematically negative in 16 patients with non-invasive forms of aspergillosis (namely aspergilloma and chronic aspergillosis). Remaining PCR-positive after a period of 14 to 20 days of treatment was related to poor outcome at 30 and 90 days. Our results also indicate that, unlike the determination of the galactomannan index, the initial fungal load as determined by PCR was highly predictive of 90-day mortality, with the rate of this latter being 15.8% for patients with less than 150 copies/mL vs 73.2% for patients at or above that cut-off (p