Real-time polymerase chain reaction testing for early detection of invasive aspergillosis in patients with febrile neutropenia

Abstract

Introduction: The identifi cation of patient risk factors for the development of invasive aspergillosis (IA) has led to more effective use of antifungal prophylaxis, empirical therapy, and preemptive treatment in targeted populations. [1,2]. However, IA breakthrough infections and the continued diffi culty in making an early diagnosis contribute to a mortality rate of more than 50%. Lung biopsy to demonstrate fungal elements and/or growth remains the diagnostic gold standard, but biopsy is often precluded in seriously ill thrombocytopenic patients. As earlier IA diagnosis is clearly linked to improved survival, recent efforts have focused on developing noninvasive techniques to detect infection at its earliest stages (ie, before the patient presents with symptoms) [3]. These include high-resolution CT (HRCT) scans of the chest and assays to detect circulating fungal cell wall antigens, such as galactomannan (GM) and (1→3)-β-D-glucan [3–5]. Although HRCT may identify characteristic IA lesions earlier than previous imaging techniques, it still only detects lesions when the disease is already far advanced. Also, because a variety of pulmonary abnormalities are common in high-risk patients, the HRCT lacks specifi city for IA. Serial serum GM tests have high sensitivity and specifi city in some high-risk populations, but limitations include false positives with certain β-lactam antibiotics (which are commonly used for empiric treatment of fever and neutropenia) and false negatives with antifungal prophylaxis [4]. Recently, molecular methods to detect fungal nucleic acids (DNA specifi cally) in blood or serum via polymerase chain reaction (PCR) techniques have been applied to the diagnosis of Candida and/or Aspergillus [6–8]. Generally, serial detection of Aspergillus DNA by PCR has had low predictive value because of limited use of the test to times just before the diagnosis of IA. However, the high negative predictive value (NPV) of Aspergillus PCR tests has been noted, helping to rule out IA. It was hypothesized in the Cuenca-Estrella et al. study that if serial Aspergillus PCR tests are performed very early (ie, during the period of fever and neutropenia following intensive chemotherapy), then the diagnostic value of the test might be increased.