Diagnosis of invasive mold diseases in patients with hematological malignancies using Aspergillus , Mucorales, and panfungal PCR in BAL

Background Accurate diagnosis of invasive mold diseases ( IMD ) remains challenging. Here, the performance of panfungal PCR , Aspergillus and Mucorales PCR in bronchoalveolar lavage ( BAL ) was evaluated. Methods We conducted a single‐center study including 167 hematologic patients at risk for IMD with BAL performed 2011‐2014. Diagnostic performance of single tests ( Aspergillus ‐, Mucorales‐, and panfungal PCR , galactomannan ( GM )≥0.5 and ≥1, culture/cytology) or in combination was calculated for predicting IMD comparing proven/probable or proven/probable/possible IMD vs no IMD , respectively. Results IMD was classified as proven (n = 6), probable (n = 31), possible (n = 29) and no IMD (n = 101) according to EORTC / MSG criteria. GM  ≥ 0.5 in BAL showed the highest sensitivity with 81% for diagnosing IMD whereas the other tests only 5%‐35%. By contrast, specificity was highest for panfungal PCR with 99% and GM  ≥ 1, Mucorales and Aspergillus PCR reached specificity ≥91%. When combining the tests, GM  ≥ 0.5 and panfungal PCR show a sensitivity and specificity of 87% and 78% for IMD or with Aspergillus PCR a sensitivity and specificity of 88% and 72% for invasive pulmonary aspergillosis, respectively. Including possible IMD patients did not improve the sensitivity of PCR s. In probable/proven IMD patients, the addition of panfungal PCR resulted further in detection of Fusarium species and Alternaria species, and the Mucorales PCR was positive in 2 probable IMD cases. Conclusion This study illustrates that the diagnosis of IMD is still very problematic and lacks objectivity. Together with GM in BAL , the PCR s may prove an addition to the current available diagnostic armamentarium in IMD because of their ability to identify molds on a species level.