Prospective clinical evaluation of lower cut‐offs for galactomannan detection in adult neutropenic cancer patients and haematological stem cell transplant recipients

Abstract

SummaryThe recent advent of an improved commercial serum enzyme-linked immunosorbent assay (ELISA) for the detection of circulating galactomannan (GM), a major constituent of Aspergillus cell walls, has contributed to the diagnosis of invasive aspergillosis (IA) in many haematology and transplant centres. However, the optimal threshold for positivity remains a matter of debate. We prospectively evaluated the impact of lowering the cut-off in 124 neutropenic episodes with a high pretest probability for IA. Two new cut-off points, lower than previously accepted, are proposed: (a) a 'static' cut-off at 0AE8 and (b) a 'dynamic' cut-off at 0AE5. A single assay with an optical density (OD) index ‡0AE8 warrants the initiation of anti-Aspergillus therapy. A further lowering of the 'static' threshold seems not clinically feasible given the drop in positive predictive value (PPV). However, the demonstration of at least two sequential sera with an OD ‡0AE5 ('dynamic' threshold) increased the specificity and the PPV to 98AE6% and the efficiency to 98%. Applying both cut-offs to a subgroup of 21 'possible' fungal infections further identified and upgraded six cases of IA. However, the clinical benefit of lower cut-offs (particularly for earlier diagnosis) depends upon the kinetics of antigenaemia and the intensity of serum sampling.

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“…Similar results have been found by Maertens et al, Kawazu et al and Lai et al [14,15,16]. Cut off values have also been reviewed by Mycoses study group.…”

Novel Antifungal Drugs Against Fungal Pathogens: Do They Provide Promising Results for Treatment?

“…Aspergillus galactomannan antigen test was performed using Platelia commercial enzyme immunoassay kit (Platelia Aspergillus EIA; Bio-Rad Laboratories, Marnes-la-Coquette, France). Blood samples of patients were analyzed twice weekly and results were computed as an index in which values of C0.5 were considered as positive relative to an optical density of the control sample measured with a semiautomatic analyzer (Behring ELISA processor III; Dade Behring, Marburg, Germany) [9]. Possible causes of false-positive and negative results were eliminated.…”

Diagnosis of Aspergillus niger Peritonitis in a Peritoneal Dialysis Patient by Peritoneal Galactomannan and β–d-Glucan Detection

“…Most instances are external breaks associated with mechanical or chemical stress (1)(2)(3). Internal breaks are relatively uncommon, but they can be caused by product defects, accidental needle-stick injury, the catheter becoming brittle with aging, and the intrinsic properties of polyurethane (4)(5)(6)(7)(8). In particular, it has been widely accepted that polyurethane catheters are highly biocompatible, but vulnerable to various types of physical and chemical stress that lead to polyurethane degradation (7,8).…”

“…In 2003, the US Food and Drug Administration approved the use of a double-sandwich GM enzyme immunoassay (Platelia Aspergillus EIA: Bio-Rad Laboratories) for the diagnosis of invasive aspergillosis in adult patients (7). The double-sandwich ELISA for detection of GM is reported to have high sensitivity and high specify for invasive aspergillosis when a cut-off value of 0.8 ng/mL is used (8).…”

“…Internal breaks are relatively uncommon, but they can be caused by product defects, accidental needle-stick injury, the catheter becoming brittle with aging, and the intrinsic properties of polyurethane (4)(5)(6)(7)(8). In particular, it has been widely accepted that polyurethane catheters are highly biocompatible, but vulnerable to various types of physical and chemical stress that lead to polyurethane degradation (7,8). Moreover, Weaver et al (9) reported that mupirocin containing polyethylene glycol causes structural changes in PD catheters and that the resulting abnormalities increase in severity with longer duration of mupirocin use.…”