Objectives: In high-risk patient cohorts, such as patients after allogeneic stem-cell transplantation, or patients with acute leukaemia, early diagnosis of invasive fungal infections (IFIs) is essential, as delayed or missing diagnosis of IFI results in increasing rates of mortality. Current non-culture based, diagnostic tests for systemic fungal infections include measurement of Aspergillus galactomannan (GM) and polymerase chain reaction (PCR) assays for Pneumocystis, Aspergillus or Candida DNA. The aim of this study was to investigate the diagnostic utility of both the aspergillus galactomannan (GM) antigen and the fungal PCR assays in the diagnosis of IFI in high risk febrile neutropenic cancer patients. Methods: During one year period, 40 febrile neutropenic (FN) cases at high risk for developing IFI while receiving chemotherapy were investigated at Gazi University Faculty of Medicine. These patients were subjected to clinical evaluation, chest CT scan, conventional blood cultures for bacterial and fungal pathogens, aspergillus GM antigen detection and PCR assay utilizing Pneumocystis, Candida and Aspergillus primers. Patients were screened twice a week by PCR and antigen testing during fever and were followed-up for a minimum of 1 year. Of the 40 cases, 3 were proven IFI; whereas 7 cases were probable and 30 cases were possible IFI. Results: Aspergillus antigen test showed a sensitivity of 75%, specificity of 60%, positive and negative predictive values of 50% and 85%; respectively. Based on positive results for proven/probable IFI and compared to culture results, Candida, Aspergillus and Pneumocystis PCR assays showed sensitivity, specificity, positive and negative predictive values of between 70-75%, 90-92%, 80-84% and 80-87%; respectively. Conclusions: The introduction of a comprehensive diagnostic strategy to exclude invasive fungal infection in high-risk patients with haematological malignancy can result in improvements in clinical management. These molecular assays provide high potential in terms of sensitivity and specificity, but vary widely in their feasibility and up to now have not been standardised. The results of PCR assay was reasonably specific but not very sensitive and had a chance of missing the diagnosis of IFI. The PCR assay seems a promising test for objectively defining IFI, but is not recommended as the only tool for diagnosing IFI. Combining microscopy, culture, and PCR may improve the diagnostic outcome.
Full conference title:
20th European Congress of Clinical Microbiology and Infectious Diseases
- ECCMID 20th (2010)