Background Invasive fungal disease (IFD) frequently occurs in febrile neutropenic haemato-oncology patients (NHP). Until 2012 no biomarkers were available for the diagnosis of IFD in our Trust. The neutropenic fever pathway was modified to include serial serum Aspergillus galactomannan (GM), serum Aspergillus PCR (APCR) from national reference laboratory and Bronchoalveolar lavage (BAL) GM and APCR.
We compared 299 NHP who were investigated with the original pathway between October 2009 and April 2012 with 307 NHP investigated with the novel pathway between April 2013 and 2015. Primary end point was non-inferiority of novel pathway in terms of 12 month mortality. Secondary outcomes were 30 day mortality, length of treatment, length of stay and confidence of diagnosis based on EORTC/MSG criteria1 and concordance of the different biomarkers.
Method Prospective patients (2013–15 cohort) were identified from ward lists. Retrospective patients (2009–12 cohort) were identified from haemato-oncology patients who had had blood cultures and were co-incidentally found to be neutropenic. Medical notes, drug charts, discharge letters and microbiology results were reviewed.
Results The 2 cohorts were well matched in terms of haemato-oncology diagnosis. The 2009/12 cohort included 561 episodes, with 333 CT chests and 62 bronchospies compared to 508 episodes, 288 CT chests and 86 bronchoscopies in 2013/15 group. 12 month mortality was 42% in 2009/12 versus 34% in 2013/15 cohort. 30 day mortality was 11% for both cohorts. There was no significant difference in length of antifungal treatments, although 24% switched to voriconazole following positive biomarkers.
Concordance between serum and BAL GM was 14.8% and APCR was 6.3%. Concordance between serum GM and APCR was 7% and between BAL GM and PCR was 41%.
Confidence in diagnosis of IFD increased with the novel pathway See Figure 1.
Conclusion The introduction of a novel NF pathway was found to be non-inferior in terms of 12 month and 30 day mortality. Although there was increased confidence in the diagnosis of IFD, this did not translate to reduced antifungal treatment, although it did influence switching to voriconazole and secondary chemoprophylaxis. Negative serum GM and PCR did not rule out the diagnosis of IFD and BAL biomarkers were more sensitive than serum ones.