Michael Kleinberg

The diagnosis of invasive pulmonary aspergillosis is challenging. It is unclear whether galactomannan (GM) results from bronchial wash (BW) and bronchoalveolar lavage (BAL) samples differ in a clinically meaningful way. Ninety-six paired (BAL and BW) samples from 85 patients were included. The average age was 53 years, 61 % of the patients were male, and 74.1 % had an underlying diagnosis of AML/MDS (ALL 7.1 %, other hematologic malignancy 18.8 %). 57 (67.1 %) patients were neutropenic, and 56 (65.9 %) patients were receiving mold-active drugs at least 48 h prior to bronchoscopy. The overall agreement between GM detection from BW and BAL was 63.5 % (K = 0.152; 95 % CI 0.008–0.311) and 73 % (K = 0.149; 95 % CI 0.048–0.348) at cut off ≥0.5 and ≥1.0, respectively. Among 43 positive samples, using a GM cut-off of 0.5, 39 (90.5 %) were positive in BW samples whereas 12 (29.3 %) were positive in BAL samples. The median level of GM in BW (0.28) samples was significantly higher than in BAL (0.20) samples among 53 samples with negative results (P = 0.001). There was no statistically significant difference in the median GM values between the BW and BAL samples with positive results (P = 0.08). There was no significant difference in GM detection between samples with positive and negative results with regard to antifungal, beta lactam antibacterial treatment or neutropenia (60.5 vs 56.6 %; 53.9 vs 46 %; 65.1 vs 54.7 %, respectively). This retrospective study examining two collection techniques suggests that BW may have higher diagnostic yield compared to bronchoalveolar lavage for GM detection.

Aspergillosis is a potentially lethal infection of immunocompromised patients. Until 10 years ago, antifungal therapy was largely limited to amphotericin B deoxycholate. Perceived poor response rates and inherent toxicities with amphotericin B deoxycholate were a major stimulus for the development of newer antifungals, including lipid-formulated amphotericin B, broad spectrum azoles, and echinocandins. Response rates to antifungals are highly dependent on the underlying diagnosis and degree of immune suppression of the patient. Patients at highest risk of death from aspergillosis also have very high mortality rates from other causes as well. Outcomes reported in historical literature reviews fail to distinguish between overall mortality and death attributable to aspergillosis. While this distinction can often be difficult to assess clinically, the net effect is to underestimate the therapeutic success rates of antifungals. The CLEAR (Collaborative Exchange of Antifungal Research) project started as a post approval survey to monitor clinical use of amphotericin B lipid complex (ABLC). The scope of the CLEAR project included collection of clinical data to assess outcomes in patients with invasive fungal infections treated with ABLC. Clinical data from more than 3500 patients were entered into the CLEAR database. Outcomes were assessed for 509 patients with documented aspergillosis and complete data records. Overall response rate was 63% (cured/improved/stable) with site-specific response rates of 61%, 59%, and 32% for lung, sinus, and central nervous system infections, respectively. Solid organ transplant recipients had higher response rates than patients with hematological malignancies. Bone marrow transplant recipients had the lowest response rates. Clinical response rates with ABLC reported in the CLEAR trial are higher than response rates reported for amphotericin B deoxycholate in other trials. Since it is unlikely we will see any new comparative Phase III trials for aspergillosis, CLEAR-type outcome studies will prove useful for the foreseeable future to guide clinical management of aspergillosis.