Abstract
This study aimed to investigate fungal agents in febrile neutropenic patients with hematological malignancies. Direct microscopy and cultures were performed on clinical samples collected from febrile neutropenic episodes. The galactomannan (GM) antigen was tested using enzyme-linked immunosorbent assays, and Aspergillus fumigatus and Candida albicans deoxyribonucleic acid (DNA) assessed using real-time polymerase chain reaction (PCR) in consecutive serum samples. Of the 199 episodes investigated, 1.5% were classified as definite invasive aspergillosis (IA), 4.0% as IA with high probability, and 4.0% as IA with low probability. Additionally, candidaemia was detected in eight episodes (4.1%). The GM antigen was found negative for 86.4% of episodes, as one positive for 7.0% of episodes, as two or more consecutive positives for 5.5% of episodes, and as positive in any two serum samples in 1.0% of episodes. While no C. albicans DNA was detected in 98.5% of 199 episodes, one positive result was obtained in 1.0% of episodes, and two or more consecutive positives in 0.5% of episodes. A. fumigatus PCR results were found negative in 81.9% of episodes, as one positive in 16.1% of episodes, as positive in any two serum samples in 1.0% of episodes, and consecutively positive in 1.0% of episodes. GM antigen tests were found consecutively positive in all three patients diagnosed as having definite IA. These findings indicate that conventional, serological, and molecular methods should be used in combination to detect fungal agents in febrile neutropenic patients.
Highlights
Fungal infections are among the most important causes of mortality and morbidity in neutropenic patients
Of a total of 199 neutropenic episodes investigated, according to the classification by the EORTC/Mycoses Study Group, definite invasive aspergillosis (IA) was detected in three (1.5%) episodes by histopathological observation of hyphal structures with septae in brain biopsy samples; eight (4.0%) neutropenic episodes were identified as high-probability IA, and eight (4.0%) as low-probability IA, whereas the remaining 180 (90.5%) episodes were not found at risk of IA
No growth occurred in blood cultures from 124 (63.9%), out of 194, episodes, whereas bacterial growth was detected from 62 (32%) episodes and the growth of various Candida species from seven (3.6%) episodes
Summary
Fungal infections are among the most important causes of mortality and morbidity in neutropenic patients. There is a high mortality rate in neutropenic patients with fungal infections, e.g. 50% with Candida infections [3], and Submitted: 4 March 2015 /Accepted: 14 April 2015. Previous studies showed that early treatment of fungal infections leads to better prognosis in neutropenic patients. Early diagnosis and treatment of these infections are of crucial importance. An established diagnostic method for early diagnosis of IFIs, with adequate sensitivity and specificity, is lacking [5]. Failure to adequately apply invasive diagnostic methods in certain cases, for example, in the absence of clinical findings and the presence of thrombocytopenia in patients with hematological malignancy, together with long waiting times before culture results are obtained, leads to significant delays in initiating treatment. The serological detection of fungal antigens and the use of molecular methods to test for nucleic acids have led to
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